Pharmacokinetics, pharmacodynamics, and safety of esomeprazole injection/infusion in healthy Chinese volunteers: A five-way crossover study

Authors

  • Hong Yang,

    1. Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
    • These authors contribute to this work equally.
  • Jingnan Li,

    1. Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
    • These authors contribute to this work equally.
  • Qian Zhao,

    1. Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Ji Li,

    1. Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Kai Shen,

    1. Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Xiaoou Yang,

    1. Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Ji Jiang,

    1. Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Pei Hu,

    1. Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    Search for more papers by this author
  • Jiaming Qian

    Corresponding author
    1. Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China
    • Correspondence

      Dr Jiaming Qian, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China. Email: qjiaming1957@aliyun.com and Dr Pei Hu, Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China. Email: pei.hu.pumc@gmail.com

    Search for more papers by this author

Abstract

Background

Esomeprazole provides effective and long lasting inhibition of gastric acid secretion. However, the pharmacokinetics and pharmacodynamics of intravenous esomeprazole in the Chinese population remain unclear.

Aim

To compare the pharmacokinetics and pharmacodynamics of intravenous esomeprazole (injection and infusion) and their clinical safety and tolerability in healthy Chinese subjects.

Methods

A randomized, single-center, open-label, five-way crossover study was conducted in 20 healthy volunteers. CYP2C19 metabolizer genotype and Helicobacter pylori status were examined. Five dosing regimens were used: single 40 mg injection, 40 mg infusion every 12 h, 40 mg infusion followed by continuous infusion at 8 mg/h, 80 mg infusion followed by continuous infusion at 4 or 8 mg/h. Intragastric pH was recorded within 24 h. Plasma concentration-time curve, maximum plasma concentration (Cmax), steady state concentration, and total plasma clearance were determined. Adverse events were also recorded.

Results

Continuous infusion resulted in a higher mean area under the curve and Cmax than injection. There were no significant differences among the four infusion groups in terms of percentages of time at pH > 4, > 5, > 6, > 7 within 24 h and pH > 6 within the first 3 h. There were no significant differences in pharmacokinetic or pH values among variants of CYP2C19 genotype. The pH value within 24 h was unaffected by H. pylori infection in subjects with continuous infusion.

Conclusions

Esomeprazole administrated by infusion produces better pharmacokinetic and intragastric pH profiles compared with those by injection. The optimal administration schedule for esomeprazole in Chinese subjects is infusion with 40 mg/12 h.

Ancillary