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Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

以干细胞源性肝细胞作为药物诱导性肝损伤预测模型:我们成功了吗?

Richard Kia, Rowena L. C. Sison, James Heslop, Neil R. Kitteringham, Neil Hanley, John S. Mills, B. Kevin Park & Chris E. P. Goldring

在各种药物不良反应中,药物诱导性肝损伤是患者患病和死亡的突出原因。然而,目前为安全性评估而开发的已有肝脏模型系统的实用性和重要性均有限,因为它们不能对功能齐全的肝细胞进行完整的概括,也不能充分代表群体中存在的基因多态性。干细胞研究的迅速发展提高了利用人多能干细胞弥补这一空白的可能性。通过人成熟体细胞的改编生成人诱导性多能干细胞也能为评估药物安全性和毒理学进行体外疾病建模。这将使我们更好地理解疾病进程,从而促进对新治疗靶点的鉴定。本综述重点分析了从人多能干细胞取得肝细胞潜在用于肝毒性评估的工作现状,旨在探明该领域的未来研究方向。

Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

心血管疾病治疗中的干细胞源性内皮细胞:治疗前景

Daniel M. Reed, Gabor Foldes, Sian E. Harding & Jane A. Mitchell

我们认为干细胞疗法和器官再生技术将成为人类疾病治疗的主流方法。分布于身体每一条血管管腔表面的内皮细胞是任何器官再生项目中不可或缺的组成要素。有潜在治疗作用的内皮细胞类型有许多,包括胚胎干细胞、成体祖细胞和诱导型多能干细胞衍生性内皮细胞及宿主血管细胞。那些能使每种细胞类型在治疗中发挥潜在用处的特征(有利和不利特性)是需要考虑的重要因素。干细胞生物学领域就生成内皮细胞的方案而言已经取得长足的发展。然而,明显而迫切需要了解的知识是这些不同来源的内皮细胞如何行使内皮功能 及其受炎症和动脉硬化的影响程度。此外,干细胞应用于临床试验时,取得细胞(从而使用细胞的特异性基因型)、应用细胞、细胞定量和/或评估细胞自身特性相关疗效的方式几乎不存在共通之处。本综述将讨论心血管疾病细胞疗法中的上述问题和其他与干细胞源性内皮细胞相关的一些问题。

Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

人干细胞源性星形胶质细胞和它们在研究神经变性中Nrf2介导性神经保护通路和治疗学中的应用

Kunal Gupta, Siddharthan Chandran & Giles E. Hardingham

神经胶质细胞,包括星形胶质细胞,由于其在神经元功能和存活调节中的作用而日渐居于神经变性研究中的前列。增强对潜在疾病机制的理解,包括细胞环境在神经变性中发挥的作用,这是对这些当前无法治愈的疾病进行治疗开发的核心。在这些努力中,那些能更接近地复制人类认知功能的实验模型在模型生物与患者试验中有潜力促进实验研究之间的转换。我们在本综述中讨论了星形胶质细胞在神经变性疾病中越来越大的作用,以及为何人多能干细胞生成的星形胶质细胞可以作为分析星形胶质细胞信号和神经元功能影响的有用工具。

Current and emerging antiviral treatments for hepatitis C infection

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

现有和新兴的丙型肝炎抗病毒疗法

Joseph S. Doyle, Esther Aspinall, Danny Liew, Alexander J. Thompson & Margaret E. Hellard

新批准的丙型肝炎病毒HCV直接作用抗病毒药能治疗多达75%的慢性基因型-1(欧洲和北美的主要HCV菌株)感染患者。新兴的抗病毒疗法可望进一步增强病毒反应,并改善耐受性和缩短疗程,也将潜在消除干扰素应用的必要性。本综述的重点是当前标准治疗中应用的几种主要治疗药,包括替拉瑞韦(telaprevir)和波西普韦(boceprevir)。还将评估新药的作用机制、到目前为止的开发进度和研究中所见的反应率。最后,将讨论不久的将来结合药物和无干扰素疗法的治疗策略,及这些治疗针对哪些患者将有可能最成功。

Overview of pharmacoeconomic modelling methods

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

药物经济学建模方法概述

Zanfina Ademi, Hansoo Kim, Ella Zomer, Christopher M. Reid, Bruce Hollingsworth & Danny Liew

在当前这个医疗保健成本迅速增长的大气候下,药物经济学的重要性日益突显,但是绝大部分临床医生对药物经济学方法的知识还很有限。本综述介绍和概述了药物经济学建模的一些常用方法:决策分析,Markov模型,折现和通过蒙特·卡罗(Monte Carlo)模拟法进行不确定性分析。本文最后将对如何阅读和评价已发表的药物经济学分析文章提出一个方法建议。

The Hypertension in the Very Elderly Trial – latest data

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

高龄老年高血压试验—最新资料

Omar Mukhtar & Stephen H. D. Jackson

高血压的早期试验以五六十岁这个年龄阶段的成年人为主要对象。然而,随着时间的推移,人们为更年长成年患者的治疗扩大证据基础作出了不懈的努力。2008年,高龄老年高血压试验(Hypertension in the Very Elderly Trial)的资料发表了,这些资料表明,八旬老人在死亡率和患病率方面可以从抗高血压治疗中显著受益。最近又有更多的一些关于该群体的资料被发表出来,这些资料认为,适当的抗高血压疗法能减少认知功能损害和骨折事件,而对主要研究为期1年的开放性延伸研究确认了许多原始试验中的发现。本综述概括介绍了高龄老年高血压试验,同时也对最近的研究资料进行了一个松散的评估。

ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

ICH E14 Q & A (R1) 文件:对全面QT研究最新建议的几点看法

Rashmi R. Shah1 & Joel Morganroth

国际协调会议(ICH)指南——ICH E14——针对临床“全面QT/QTc(TQT)研究”提出了关于药物开发过程中评估其QT敏感性的建议。也设立了一个执行工作组(IWG)来协助主办者解决和澄清不确定性和含糊不清的问题。2012年4月,IWG在其2008年版“问与答”文件的基础上进行了更新,以解释一些新增的问题,包括研究人群的性别,以适当方式评估晚期临床开发中的QTc变化,和校正被测QT间期的推荐方法。本评论提供了作者对这些问题的观点,并在适当的方面提出了一些的建议。有证据表明(1)女性中观察到的更大的QT作用并不完全与药物暴露的差异 相关,(2)对被测定QT间期以Fridericia法进行校正适于大部分TQT研究——我们简短综述了与此有关的证据。在有进一步的不同证据之前,我们建议TQT研究中应平衡性别表现,除非有其他理由,并建议对于实证研究应通过常见的人口学变量包括性别和种族等对关键资料进行亚群分析。我们对晚期临床试验中的ECG监测提供了一个总体方案,我们认为,当一项TQT研究为实证研究时,虽然在晚期临床试验中对ECGs的严格监测和集中判读是规范做法,但是也有其他情况需要高优质的ECG判读。因此,局部判读ECGs只有在ECG数据的准确性和高质量有保证时才可被 接受。

A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

有关华法林换药后口服Xa因子抑制剂——依度沙班(edoxaban)——的安全性、药代动力学和药效学的一项随机试验

Jeanne Mendell, Robert J. Noveck & Minggao Shi

    关于该课题的已知结论

  • 维生素K拮抗剂(VKAs)抗凝预防被建议用于防止有房颤风险的患者发生卒中和全身性栓塞事件以及治疗深静脉血栓形成。
  • VKAs与不可预测的药代动力学和药效学及治疗指数窄等多方面的局限性相关。
  • 新型口服抗凝药,如直接Xa因子(FXa)抑制剂正在出现,患者从VKA转向这些新一代抗凝药需要相关的指导信息。

    本研究的新发现

  • 这项针对停止华法林治疗(国际标准化比值[INR] 为2.0至3.0)24小时后以60 mg直接FXa抑制剂依度沙班单次给药的随机、安慰剂对照研究表明,就生物标志物而言,依度沙班似乎在健康志愿者中有良好的耐受性,能维持持续的抗凝作用而不过度凝血的风险。
  • 华法林最后一次给药(INR为2.0至3.0)24小时后应用依度沙班后,与安慰剂相比,前者使INR、凝血酶原时间和其他生物标志物出现瞬时性增加,以依度沙班给药2小时后最为明显。在华法林最后一次给药后48小时,安慰剂组的INR值已经低于华法林的治疗范围(即INR为2.0)。
  • 至少在最后一次华法林给药24小时后启动依度沙班给药似乎能维持抗凝固作用而不会增加过度凝血的风险,但是关于最佳给药时间窗的进一步评估将在针对房颤患者进行的3期临床研究中进行。

Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

健康志愿者应用治疗浓度和超治疗浓度的艾塞那肽不会延长QTc间期

Börje Darpö, Philip Sager, Leigh MacConell, Brenda Cirincione, Malcolm Mitchell, Jenny Han, Wenying Huang, Jaret Malloy, Christine Schulteis, Larry Shen & Lisa Porter

    关于该课题的已知结论

  • 此前有研究表明,治疗浓度的艾塞那肽(exenatide)不会延长QTc间期。对于能增加心率的药物,确定其QTc作用的最佳方法仍然是一个重要的科学问题。

    本研究的新发现

  • 本研究表明,静脉输注超治疗浓度的艾塞那肽不会延长QTc间期。值得注意的是,本研究论证了对本身有心率作用的药物进行QT评估时采取特定研究程序和前瞻性地确定最适当的心率校正法的一些方法,这些方法应该有广泛的适用性。

A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

通过健康志愿者中的碘海醇和对氨基马尿酸盐测定评估多鲁拉韦 (dolutegravir)肾功能作用的1期研究

Justin Koteff, Julie Borland, Shuguang Chen, Ivy Song, Amanda Peppercorn, Takaaki Koshiba, Courtney Cannon, Heather Muster & Stephen C. Piscitelli

    关于该课题的已知结论

  • 在多鲁拉韦德开发过程中,临床试验观察到血清肌酐的小幅可逆性升高。这些变化与体外研究资料一致,表明多鲁拉韦 (DTG;S/GSK1349572)是有机阳离子转运体-2(OCT2)的抑制剂。
  • 与其他药剂如三甲氧苄胺嘧啶(trimethoprim)和甲腈咪胍(cimetidine)等一样,这种快速起效和小幅平均肌酐升高而无推进的模式是经OCT2的典型肌酐分泌阻断作用。
  • 本研究的目的是描述DTG治疗期间观察到的血清肌酐升高机制,尤其是阐释对肾小球滤过率的作用。

    本研究的新发现

  • 一些体外资料表明:临床相关浓度的DTG是人OCT2的强效抑制剂;与安慰剂相比50 mg的DTG每天给药一次和两次均对肾小球滤过率无作用。本研究的结果支持这些临床资料。
  • 这些资料进一步表明,DTG临床研究中观察到的可逆性肌酐升高与近端肾小管中OCT2的非病理性抑制有关,这是对肌酐肾脏处理的一个良性作用。

Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

神经心理测量与依法韦仑单次口服给药后的药代动力学和药效学相关

Daniel H. Johnson, Tebeb Gebretsadik, Ayumi Shintani, Gail Mayo, Edward P. Acosta, C. Michael Stein & David W. Haas

    关于该课题的已知结论

  • 含有依法韦仑的治疗方案虽然在通常情况下是安全有效的,但是其与中枢神经系统副作用的高发率相关,尤其是在给药的头几天或头几个星期。这些副作用不一致地与血浆中的依法韦仑浓度及与CYP2B6遗传学相关。CYP2B6的遗传学与依法韦仑的药代动力学相关。

    本研究的新发现

  • 本文是唯一的一项描述依法韦仑单次给药6小时内依法韦仑药代动力学和药效学与神经认知功能主观和客观测量之间相关性的研究。本研究通过非优势手钉板测试(non-dominant hand grooved pegboard test)表明,依法韦仑的药代动力学和神经认知功能副作用高度相关。神经认知测试与CYP2B6基因型之间的相关性很可能反映了基因型与清除率的相关性。

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

基于总血浆浓度预测胃肠道间质瘤患者的游离伊马替尼浓度

Amina Haouala, Nicolas Widmer, Monia Guidi, Michael Montemurro, Serge Leyvraz, Thierry Buclin, Chin B. Eap, Laurent A. Decosterd & Chantal Csajka

    关于该课题的已知结论

  • 伊马替尼与α1-酸性糖蛋白结合的变异性可能影响其活性,因为只有游离药才可能平衡细胞内环境而发挥其药理学作用。
  • 虽然目前有人建议对伊马替尼总浓度进行治疗药监测,但鉴于成本和技术问题,通常没有例行测定游离浓度。

    本研究的新发现

  • 本研究首次使鉴定总体和未结合态伊马替尼浓度的人群药代动力学特征和基于总浓度和α1-酸性糖蛋白水平有把握地预测伊马替尼的游离浓度成为可能。

Predicted metabolic drug clearance with increasing adult age

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

对成年人随年龄增长的代谢药物清除率预测

Thomas M. Polasek, Farhaan Patel, Berit P. Jensen, Michael J. Sorich, Michael D. Wiese & Matthew P. Doogue

    关于该课题的已知结论

  • 在老年人中,经CYP酶代谢的药物清除率会降低。
  • 体外-体内外推结合基于生理学的药代动力学(IVIVE-PBPK)模型和模拟被广泛用于预测代谢药物清除率。

    本研究的新发现

  • 与大量有关CYP酶代谢药物的临床文献一样,IVIVE-PBPK模型和模拟运用Simcyp®预测的老年人体重正常者的代谢清除率比年轻成人低20~40%。
  • 这个预测是用于代谢药物清除率体外-体内外推的生理参数年龄相关降低的直接结果,即每克肝组织的平均肝微粒体蛋白、肝重量、肝血流和人血清白蛋白浓度。
  • 代谢药清除率随着成人年龄增大而降低的预测,对于那些有不同肝提取率和蛋白结合特点的药物也一样,并且似乎对药物特异性生理化学参数、负责代谢的CYP酶和它们对代谢清除率的分数作用没有依赖性。
  • 老年人中的清除率降低可能对所有只能被CYP酶消除的药物都是一样的。

Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

拮抗剂ABT-102对健康志愿者体温的作用:三项1期试验的药代动力学/药效学分析

Ahmed A. Othman, Wolfram Nothaft, Walid M. Awni & Sandeep Dutta

    关于该课题的已知结论

  • ABT-102在临床前疼痛模型中是一种有强劲镇痛活性的选择性TRPV1拮抗剂。
  • 越来越多的证据表明,TRPV1通道参与了体温调节。
  • TRPV1拮抗剂能升高灵长类和非灵长类的体温。

    本研究的新发现

  • 我们在本报告中对ABT-102的人体体温作用提供了一个全面的人群药代动力学/药效学分析,该分析由来自三个1期试验的巨大数据集组成,这些1期试验广泛监测了ABT-102治疗和洗脱期间的体温。

Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

蓝莓果汁对人类志愿者丁螺环酮和氟吡洛芬清除率的作用

Michael J. Hanley, Gina Masse, Jerold S. Harmatz, Paul F. Cancalon, Gregory G. Dolnikowski, Michael H. Court & David J. Greenblatt

    关于该课题的已知结论

  • 许多柑橘属果实和果汁能体外抑制人类细胞色素P450(CYPs)的活性。
  • 一些体外研究显示营养成分和天然产品对CYP有抑制作用,但这种研究并非一定能预测临床药物相互作用。
  • 只有葡萄柚汁(GFJ)含有的天然物质对CYP3A有不可逆性(而不是可逆性)体外抑制作用,迄今为止只有GFJ显示能与CYP3A底物产生显著的体内药物间相互作用。

    本研究的新地现

  • 低浓度的蓝莓果汁(BBJ)能产生对CYP3A和CYP2C9活性的体外抑制作用。
  • BBJ的抑制机制是可逆而非不可逆的。
  • 在人类志愿者临床研究中,BBJ能轻微地损害CYP3A活性,但对CYP2C9活性没有明显的抑制作用。
  • 与BBJ和经CYP3A或CYP2C9代谢的底物药相关的药物间相互作用风险,如果说有的话,也可以说是非常低的。

Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

达比加群酯(Pradaxa®)在健康志愿者中联合异搏定给药后的 口服 生物利用度

Sebastian Härtter, Regina Sennewald, Gerhard Nehmiz & Paul Reilly

    关于该课题的已知结论

  • 口服前体药达比加群酯(dabigatran etexilate; DE)所得到的活性成分——达比加群(dabigatran)——是一种有强效抗血栓作用的直接、可逆性凝血酶抑制剂。
  • DE和达比加群都不经肝细胞色素P450酶的同工酶代谢,也不影响利用细胞色素P450系统的其他药物的代谢。
  • DE(但不是达比加群)是外排性转运体P-糖蛋白(P-gp)的底物,影响P-gp的药物有可能改变达比加群的生物利用度。

    本研究的新发现

  • 达比加群与P-gp抑制剂如异搏定联合应用时,其生物利用度将升高。多种因素对这种相互作用有影响:(1)两种药物的给药间隔:异搏定给药1小时后应用DE会出现达比加群暴露水平的最大升幅,而DE给药2小时后应用异搏定则几乎对暴露没有任何作用;(2)异搏定的剂型:速释剂型的作用大于缓释剂型;(3)异搏定给药:单次给药对达比加群药代动力学的作用大于多次给药。
  • 如果在空腹状态下先于异搏定2小时应用DE,那么异搏定与DE之间的相互作用将减至最小。

Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

曲马多与低血糖症:与其他二阶镇痛药的比较

Cindy Bourne, Aurore Gouraud, Amélie Daveluy, Aurélie Grandvuillemin, Pascal Auriche, Jacques Descotes, Thierry Vial & the French Association of Regional Pharmacovigilance Centres

    关于该课题的已知结论

  • 右丙氧芬(DXP)被确认为是致低血糖的可能原因,但是只有一些零星的报告描述过曲马多(TRM)有相似的不良作用。
  • 据我们所知,目前还没有大样本研究比较过患者应用这些二阶镇痛药后的低血糖发生率。

    本研究的新发现

  • 本研究的目的是描述TRM相关性低血糖症的自发性报告,将这些资料与DXP诱导的低血糖症进行比较。
  • 研究结果表明,曲马多使用者表现出的低血糖特点与DXP使用者描述的特点非常相似,其主要风险因素有老龄、糖尿病和肾功能不全。
  • 医生和患者应该被警告该潜在不良作用的存在。

External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

对新生儿应用万古霉素的人群药代动力学模型的外部评估:已发表的模型向不同临床环境的可转移性

Wei Zhao, Florentia Kaguelidou, Valérie Biran, Daolun Zhang, Karel Allegaert, Edmund V. Capparelli, Nick Holford, Toshimi Kimura, Yoke-Lin Lo, José-Esteban Peris, Alison Thomson, John N. van den Anker, May Fakhoury & Evelyne Jacqz-Aigrain

    关于该课题的已知结论

  • 新生儿应用万古霉素的人群药代动力学受到了广泛的研究。
  • 研究者对许多协变量,包括体重、胎龄和出生后年龄、肾功能、联合应用药物等,都做过评估,其中一些协变量与个体间的药代动力学差异相关。

    本研究的新发现

  • 本研究确定,测定血清肌酐浓度时采用的分析技术是影响已发表模型向不同临床环境可转移性的一个研究相关因素。
  • 研究表明,不同分析方法 [荧光极化免疫测定法(FPIA)和酶增强免疫测定法(EMIT)] 的预测能力也不一样。
  • 在未来的研究中,应该评估Jaffé速率法与酶法之间的新生儿血清肌酐浓度换算系数和分析方法的干扰和交叉反应性。

Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

哮喘儿童患者应用吸入性倍氯米松和福莫特罗压力定量吸入剂固定结合和自由结合给药的药代动力学比较

Bo L. K. Chawes, Annalisa Piccinno, Eskil Kreiner-Møller, Nadja H. Vissing, Porntiva Poorisrisak, Li Mortensen, Erik Nilson, Amalie Bisgaard, Anna Dossing, Maja Deleuran, Nanna L. Skytt, Nasim Samandari, Francesco Sergio, Giorgia Ciurlia, Gianluigi Poli, Daniela Acerbi & Hans Bisgaard

    关于该课题的已知结论

  • 丙酸倍氯米松和福莫特罗压力定量吸入剂(pMDI)的固定结合在市场上以Foster® 100/6 μg的剂型销售,用于治疗成人哮喘。Foster®现在被开发为低强度剂型(50/6 μg),为儿童哮喘患者提供合适的剂量。

    本研究的新发现

  • 本研究表明,在5–11岁的儿童哮喘患者中,丙酸倍氯米松和福莫特罗两种活性成分固定和自由结合应用后的药代动力学和药效学作用并无优劣之分。

Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

防止将阿尔茨海默病患者纳入临床试验的理由

Adeline Rollin-Sillaire, Laetitia Breuilh, Julia Salleron, Stéphanie Bombois, Pascaline Cassagnaud, Vincent Deramecourt, Marie-Anne Mackowiak & Florence Pasquier

    关于该课题的已知结论

  • 阿尔茨海默病(AD)是最常见的进行性神经退行性疾病,是老年痴呆的主要原因。由于胆碱酯酶抑制剂和美金刚的症状作用药效温和,因此亟待开发出新的AD疗法。但是AD临床试验测试对象的招募面临着许多挑战。

    本研究的新发现

  • 迄今尚无研究评估过不将AD患者纳入临床试验的主要医学和非医学原因。AD临床试验的许多参与障碍是无法改变的,尤其是缺乏研究陪伴者。然而,在大型AD研究设计中,能提高参与数量的主要因素有:(1)MRI脑白质损害的出现和(2)附加胆碱酯酶抑制剂和/或美金刚对症治疗。

Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

对德国常规实践中度洛西汀(duloxetine)治疗女性应激性尿失禁的 安全性和耐受性观察研究

Martin C. Michel, Anette Minarzyk, Inka Schwerdtner, Deborah Quail, Hans D. Methfessel & Hans-Joachim Weber

    关于该课题的已知结论

  • 度洛西汀在双盲、随机对照试验中安全性良好,但是对胺摄取抑制剂又出现了新的安全性问题,特别是有关自杀的风险。临床应用的度洛西汀剂量通常低于推荐剂量。

    本研究的新发现

  • 现实生活数据可以确定度洛西汀的耐受性和安全性,在一个包括3233例病人年的人群中未发现其有自杀风险的证据。处方的度洛西汀剂量往往低于推荐剂量,这些剂量与对照研究的不良事件性质相似但其不良事件更少。我们的平行组设计可能对其他治疗领域的观察研究也同样有价值。

What can we learn from parents about enhancing participation in pharmacovigilance?

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

药物监察中如何从患者父母获得信息以提高参与度?

Janine Arnott, Hannah Hesselgreaves, Anthony J. Nunn, Matthew Peak, Munir Pirmohamed, Rosalind L. Smyth, Mark A. Turner & Bridget Young
  • 父母向药物监察系统直接报告不良药物作用能提供重要信息,但是公众对此类方案的意识淡薄。一些研究在确定影响参与的障碍因素时从来都是以成年患者的报告为主,而没有特别关注过父母报告子女药物不良反应(ADRs)的经历。作为充当子女护理者角色的父母,对ADRs报告有其独特的视角。

    本研究的新发现

  • 我们确定了一些此前未曾报告过的影响患者父母参与系统性药物监察的障碍,包括对非专业人士提交报告是否合法的不确定性。我们也发现了一些父母报告的新奇动机,包括需要减轻负罪感。我们的发现表明,药物监察机构有必要走出仅仅是提高公众意识的框架,采取措施以授权和支持非专业人士报告ADRs的方式向公众推行他们的方案。

Statins and risk of treated incident diabetes in a primary care population

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

他汀类药物和基层医疗保健人群治疗后新发糖尿病的风险

Nur Lisa Zaharan, David Williams & Kathleen Bennett

    关于该课题的已知结论

  • 心血管病的高风险患者应用他汀类作为初级和二级预防药。
  • 最近一些随机对照试验荟萃分析显示,接受他汀类治疗后的新发糖尿病风险会升高。
  • 普通基层医疗保健人群中的新发糖尿病与他汀类治疗的潜在相关性有待进一步观察。

    本研究的新发现

  • 我们发现,基层医疗保健人群接受他汀类处方与新发糖尿病之间相关。
  • 本研究发现,与无他汀类处方者相比,接受瑞舒伐他汀(rosuvastatin)、辛伐他汀(simvastatin)和阿托伐他汀(atorvastatin)单药治疗患者的新发糖尿病会增多。
  • 除氟伐他汀(fluvastatin)之外,所有他汀类药物的整体剂量和时间作用都有显著统计学意义,而前者仅显示有时间作用。

Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

精神类药品与机动车辆事故风险:基于人群的病例对照研究

Chia-Ming Chang, Erin Chia-Hsuan Wu, Chuan-Yu Chen, Kuan-Yi Wu, Hsin-Yi Liang, Yeuk-Lun Chau, Chi-Shin Wu, Keh-Ming Lin & Hui-Ju Tsai

    关于该课题的已知结论

  • 人们早已知道精神类药品可损害认知和心理运动能力。
  • 大部分研究重点关注苯二氮卓类(BZDs)与机动车辆事故(MVAs)之间的关系。关于新精神类药品对MVAs的作用评估的现有信息很有限。

    本研究的新发现

  • 除了BZDs(包括长效型、短效型、安眠类和镇静类药物)之外,抗抑郁药(选择性5羟色胺再摄取抑制剂和三环类抗抑郁药)和Z药(Z-drugs)暴露也与MVAs风险的升高显著相关。
  • 这些发现突出表明,应用这些精神类药品的个体应该加倍注意他们的驾驶表现,以防止出现MVAs。

Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

孕前父亲药物暴露对分娩结局的作用:一项基于挪威人群数据库的 340 000名孕妇队列研究

Anders Engeland, Tone Bjørge, Anne Kjersti Daltveit, Svetlana Skurtveit, Siri Vangen, Stein Emil Vollset & Kari Furu

    关于该课题的已知结论

  • 迄今只有很少一部分(小样本)研究中采集了孕前与父亲药物摄取相关的资料。
  • 约有四分之一的父亲在配偶怀孕前3个月中有处方药物给药经历。

    本研究的新发现

  • 此项在未经选择的人群中探讨孕前短期(3个月)内父亲用药影响的独特研究未显示父亲药物暴露是不良妊娠结局的重要风险因素。
  • 我们所用的资料来自340 000名孕妇。资料数量之大,使我们能比此前更深入地研究父亲用药对后代的影响。
  • 但是在本研究人群中,有疑似致畸作用的药物的处方频率非常低。

The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

  1. Top of page
  2. Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?
  3. Stem cell-derived endothelial cells for cardiovascular disease: a therapeutic perspective
  4. Human stem cell-derived astrocytes and their application to studying Nrf2-mediated neuroprotective pathways and therapeutics in neurodegeneration
  5. Current and emerging antiviral treatments for hepatitis C infection
  6. Overview of pharmacoeconomic modelling methods
  7. The Hypertension in the Very Elderly Trial – latest data
  8. ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies
  9. A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
  10. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects
  11. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
  12. Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose
  13. Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours
  14. Predicted metabolic drug clearance with increasing adult age
  15. Effects of the TRPV1 antagonist ABT-102 on body temperature in healthy volunteers: pharmacokinetic/pharmacodynamic analysis of three phase 1 trialsTRPV1
  16. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers
  17. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects
  18. Tramadol and hypoglycaemia: comparison with other step 2 analgesic drugs
  19. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
  20. Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children
  21. Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials
  22. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice
  23. What can we learn from parents about enhancing participation in pharmacovigilance?
  24. Statins and risk of treated incident diabetes in a primary care population
  25. Psychotropic drugs and risk of motor vehicle accidents: a population-based case-control study
  26. Effects of preconceptional paternal drug exposure on birth outcomes: cohort study of 340 000 pregnancies using Norwegian population-based databases
  27. The influence of drug use in university hospitals on the pharmaceutical consumption in their surrounding communities

大学医院中的药物应用对其周边社区药品消费的影响

Adeline Gallini, Renaud Legal & Florence Taboulet

    关于该课题的已知结论

  • 医院内的医生能直接地通过启动一些疗法或间接地通过对全科医生的药物通报影响到医院外的药品消费。
  • 制药公司向医院削本出售治疗慢性病的药品,以期从社区的长期投资中获得回报。

    本研究的新发现

  • 本文首次在全国规模上测试和量化了9类竞争性药物的医院消费对日间医疗市场的影响程度。
  • 这种影响因药物类别的不同而相差悬殊,对被研究的几类心血管药(血管紧张素转换酶抑制剂、血管紧张素受体阻断剂和他汀类)影响极大。