• 1
    Knapp DR, Gaffney TE, McMahon RE. Use of stable isotope mixtures as a labeling technique in drug metabolism studies. Biochem Pharmacol 1972; 21: 4259.
  • 2
    Browne TR. Stable isotopes in pharmacology studies: present and future. J Clin Pharmacol 1986; 26: 4859.
  • 3
    Lewis GN, MacDonald RT. Some properties of pure H2H2O [8]. J Am Chem Soc 1933; 55: 30579.
  • 4
    Nelson SD, Trager WF. The use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome P450-catalyzed reactions, and mechanisms of metabolically dependent toxicity. Drug Metab Dispos 2003; 31: 148198.
  • 5
    Klein PD, Roseland Klein E. Stable isotopes: origins and safety. J Clin Pharmacol 1986; 26: 37882.
  • 6
    Lewis GN. The biology of heavy water. Science 1934; 79: 1513.
  • 7
    Pons G, Rey E. Stable isotopes labeling of drugs in pediatric clinical pharmacology. Pediatric 1999; 104: 6339.
  • 8
    Mayevsky A, Samuel D, Ortega C, Amsel G. In vivo measurement of variations in the oxygen 18 content of water in rat brain. J Appl Physiol 1975; 39: 3004.
  • 9
    Samuel D, Steckel F. Research with the stable isotopes of oxygen (O17 and O18) during 1958–1960. Int J Appl Radiat Isot 1961; 11: 190229.
  • 10
    Durso R, Evans JE, Josephs E, Szabo G, Evans B, Fernandez HH, Browne TR. Variable absorption of carbidopa affects both peripheral and central levodopa metabolism. J Clin Pharmacol 2000; 40: 85460.
  • 11
    Brenna JT, Corso TN, Tobias HJ, Caimi RJ. High-precision continuous-flow isotope, ratio mass spectrometry. Mass Spectrom Rev 1997; 16: 22758.
  • 12
    Braden B, Haisch M, Duan LP, Lembcke B, Caspary WF, Hering P. Clinically feasible stable isotope technique at a reasonable price: analysis of 13CO2/12CO2-abundance in breath samples with a new isotope selective-nondispersive infrared spectrometer. Z Gastroenterol 1994; 32: 6758.
  • 13
    Barth E, Tugtekin I, Weidenbach H, Wachter U, Vogt J, Radermacher P, Adler G, Georgieff M. Determination of 13CO2/12CO2 ratio by IRMS and NDIRS. Isotopes Environ Health Stud 1998; 34: 20913.
  • 14
    Esler MB, Griffith DW, Wilson SR, Steele LP. Precision trace gas analysis by FT-IR spectroscopy. 2. The 13C/12C isotope ratio of CO2. Anal Chem 2000; 72: 21621.
  • 15
    Castrillo A, Casa G, Palmieri A, Gianfrani L. Measuring the 13C/12C isotope ratio in atmospheric CO2 by means of laser absorption spectrometry: a new perspective based on a 2.05-microm diode laser. Isotopes Environ Health Stud 2006; 42: 4756.
  • 16
    Stellaard F, Henk E. Analytical techniques in biomedical stable isotope applications: (isotope ratio) mass spectrometry or infrared spectrometry? Isotopes Environ Health Stud 2005; 41: 34561.
  • 17
    Ververs FFT, Smeets OSNM, Schobben AFAM. Assessment of not for human use chemicals for human use [Beoordeling voor humane toepassing van chemicaliën ‘not for human use’]. Pharm Weekbl 2006; 141: 146971.
  • 18
    Malik SI, Painter MJ, Venkataramanan R, Alvin JD. Phenytoin and phenobarbital stable isotope studies in neonates. Pediatr Neurol 2003; 29: 37680.
  • 19
    Bode H, Brendel E, Ahr G, Fuhr U, Harder S, Staib AH. Investigation of nifedipine absorption in different regions of the human gastrointestinal (GI) tract after simultaneous administration of 13C- and 12C-nifedipine. Eur J Clin Pharmacol 1996; 50: 195201.
  • 20
    Fromm MF, Dilger K, Busse D, Kroemer HK, Eichelbaum M, Klotz U. Gut wall metabolism of verapamil in older people: effects of rifampicin-mediated enzyme induction. Br J Clin Pharmacol 1998; 45: 24755.
  • 21
    Ligthart-Melis GC, Van De Poll MCG, Boelens PG, Dejong CHC, Deutz NEP, Van Leeuwen PAM. Glutamine is an important precursor for de novo synthesis of arginine in humans. Am J Clin Nutr 2008; 87: 12829.
  • 22
    Andrews FJ, Griffiths RD. Glutamine: essential for immune nutrition in the critically ill. Br J Nutr 2002; 87 (Suppl. 1): S38.
  • 23
    Ligthart-Melis GC, Van De Poll MCG, Vermeulen MAR, Boelens PG, Van Den Tol MP, Van Schaik C, De Bandt J-P, Deutz NEP, Dejong CHC, Van Leeuwen PAM. Enteral administration of alanyl-[2-15N]glutamine contributes more to the de novo synthesis of arginine than does intravenous infusion of the dipeptide in humans. Am J Clin Nutr 2009; 90: 95105.
  • 24
    Browne TR, ed. Stable Isotopes in Pharmaceutical Research. Amsterdam: Elsevier, 1997.
  • 25
    Stellaard F, Kuipers F. Assessment of modes of action and efficacy of plasma cholesterol-lowering drugs: measurement of cholesterol absorption, cholesterol synthesis and bile acid synthesis and turnover using novel stable isotope techniques. Curr Drug Targets Immune Endocr Metabol Disord 2005; 5: 20918.
  • 26
    Chan DC, Watts GF, Hugh R, Barrett P, Martins IJ, James AP, Mamo JCL, Mori TA, Redgrave TG. Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test. J Lipid Res 2002; 43: 70612.
  • 27
    De Sain-Van Der Velden MG, Kaysen GA, Barrett HA, Stellaard F, Gadellaa MM, Voorbij HA, Reijngoud D-J, Rabelink TJ. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis. Kidney Int 1998; 53: 9941001.
  • 28
    De Preter V, Geboes K, Verbrugghe K, De Vuyst L, Vanhoutte T, Huys G, Swings J, Pot B, Verbeke K. The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. J Nutr 2004; 92: 43946.
  • 29
    Wachters-Hagedoorn RE, Priebe MG, Heimweg JAJ, Heiner AM, Elzinga H, Stellaard F, Vonk RJ. Low-dose acarbose does not delay digestion of starch but reduces its bioavailability. Diabetic Med 2007; 24: 6006.
  • 30
    Gerard J, Jandrain B, Pirnay F. Utilization of oral sucrose load during exercise in humans: effect of the α-glucosidase inhibitor Acarbose. Diabetes 1986; 35: 1294301.
  • 31
    Bunt JEH, Carnielli VP, Wattimena JLD, Hop WC, Sauer PJJ, Zimmermann LJI. The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes. Am J Respir Crit Care Med 2000; 162: 8449.
  • 32
    Bunt JEH, Carnielli VP, Janssen DJ, Wattimena JLD, Hop WC, Sauer PJ, Zimmermann LJI. Treatment with exogenous surfactant stimulates endogenous surfactant synthesis in premature infants with respiratory distress syndrome. Crit Care Med 2000; 28: 33838.
  • 33
    Cogo PE, Carnielli VP, Bunt JE, Badon T, Giordano G, Zacchello F, Sauer PJ, Zimmermann LJ. Endogenous surfactant metabolism in critically ill infants measured with stable isotope labelled fatty acids. Pediatr Res 1999; 45: 2426.
  • 34
    Ismail WIW, King JA, Pillay TS. Insulin resistance induced by antiretroviral drugs: current understanding of molecular mechanisms. J Endocrinol Metab Diabetes S Afr 2009; 14: 12932.
  • 35
    Rao MN, Mulligan K, Tai V, Wen MJ, Dyachenko A, Weinberg M, Li X, Lang T, Grunfeld C, Schwarz J-M, Schambelan M. Effects of Insulin-Like Growth Factor (IGF)-I/IGF-binding protein-3 treatment on glucose metabolism and fat distribution in human immunodeficiency virus-infected patients with abdominal obesity and insulin resistance. J Clin Endocrinol Metab 2010; 95: 43616.
  • 36
    Mutlib AE. Application of stable isotope-labelled compounds in metabolism and in metabolism-mediated toxicity studies. Chem Res Toxicol 2008; 21: 167289.
  • 37
    Park KB, Dalton-Brown E, Hirst C, Williams DP. Selection of new chemical entities with decreased potential for adverse drug reactions. Eur J Pharmacol 2006; 549: 18.
  • 38
    Teitelbaum DH. Parenteral nutrition-associated cholestasis. Curr Opin Pediatr 1997; 9: 2705.
  • 39
    Duro D, Duggan C, Valim C, Bechard L, Fitzgibbons S, Jaksic T, Yu Y-M. Novel intravenous 13C-methionine breath test as a measure of liver function in children with short bowel syndrome. J Pediatr Surg 2009; 44: 23640.
  • 40
    Sauter G, Berr F, Beuers U, Fischer S, Paumgartner G. Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humans. Hepatology 1996; 24: 1236.
  • 41
    Steiner SJ, Pfefferkorn MD, Fitzgerald JF, Denne SC. Effects of infliximab and parenteral nutrition on albumin and fibrinogen synthesis rates in pediatric crohn disease. J Pediatr Gastroenterol Nutr 2008; 47: 57984.
  • 42
    Hulzebos CV, Wolters H, Plösch T, Kramer W, Stengelin S, Stellaard F, Sauer PJJ, Verkade HJ, Kuipers F. Cyclosporin A and enterohepatic circulation of bile salts in rats: decreased cholate synthesis but increased intestinal reabsorption. J Pharmacol Exp Ther 2003; 304: 35663.
  • 43
    Hulzebos CV, Bijleveld CMA, Stellaard F, Kuipers F, Fidler V, Slooff MJH, Peeters PMJG, Sauer PJJ, Verkade HJ, Cyclosporine A. Induced reduction of bile salt synthesis associated with increased plasma lipids in children after liver transplantation. Liver Transpl 2004; 10: 87280.
  • 44
    Schuster D, Laggner C, Langer T. Why drugs fail – A study on side effects in new chemical entities. Curr Pharm Des 2005; 11: 354559.
  • 45
    Strong JM, Dutcher JS, Lee WK, Atkinson AJ Jr. Absolute bioavailability in man of N acetylprocainamide determined by a novel stable isotope method. Clin Pharmacol Ther 1975; 18: 61322.
  • 46
    Shibuya F, Kuramoto K, Koizumi H. Biopharmaceutical evaluation of methylcellulose as an excipient for nitroglycerin tablets. J Pharmacobiodyn 1985; 8: 3526.
  • 47
    Gammans RE, Mackenthun AV, Russell JW. Comparative bioavailability of trazodone formulations using stable isotope methodology. Br J Clin Pharmacol 1984; 18: 4317.
  • 48
    Wilding IR, Coupe AJ, Davis SS. The role of γ-scintigraphy in oral drug delivery. Adv Drug Deliv Rev 2001; 46: 10324.
  • 49
    Wilding IR, Davis SS, Hardy JG, Robertson CS, John VA, Powell ML, Leal M, Lloyd P, Walker SM. Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled-release system and as a suspension of 15N-labelled drug to healthy volunteers. Br J Clin Pharmacol 1991; 32: 5739.
  • 50
    Cummings JH, Milojevic S, Harding M, Coward WA, Gibson GR, Botham RL, Ring SG, Wraight EP, Stockham MA, Allwood MC, Newton JM. In vivo studies of amylose-and ethylcellulose-coated [13C]glucose microspheres as a model for drug delivery to the colon. J Control Release 1996; 40: 12331.
  • 51
    Schellekens RCA, Stellaard F, Mitrovic D, Stuurman FE, Kosterink JGW, Frijlink HW. Pulsatile drug delivery to ileo-colonic segments by structured incorporation of disintegrants in pH-responsive polymer coatings. J Control Release 2008; 132: 918.
  • 52
    Verbeke K, De Preter V, Geboes K, Daems T, Van Den Mooter G, Evenepoel P, Rutgeerts P. In vivo evaluation of a colonic delivery system using isotope techniques. Aliment Pharmacol Ther 2005; 21: 18794.
  • 53
    Schellekens RCA, Stellaard F, Olsder GG, Woerdenbag HJ, Frijlink HW, Kosterink JGW. Oral ileocolonic drug delivery by the colopulse-system: a bioavailability study in healthy volunteers. J Control Release 2010; 146: 33440.
  • 54
    Schellekens RCA, Olsder GG, Langenberg SMCH, Boer T, Woerdenbag HJ, Frijlink HW, Kosterink JGW, Stellaard F. Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms. Br J Pharmacol 2009; 158: 53240.
  • 55
    Alffenaar JW, Wessels AM, van Hateren K, Greijdanus B, Kosterink JG, Uges DR. Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878: 3944.
  • 56
    Slanař O, Chalupná P, Novotný A, Bortlík M, Krška Z, Lukáš M. Fatal myelotoxicity after azathioprine treatment. Nucleosides Nucleotides Nucleic Acids 2008; 27: 6615. Biochemical Pharmacology, 21 (3), pp. 425-429.
  • 57
    Press RR, De Fijter JW, Guchelaar H-J. Individualizing calcineurin inhibitor therapy in renal transplantation – Current limitations and perspectives. Curr Pharm Des 2010; 16: 17686.
  • 58
    Eidens M, Prause S, Weise A, Klemm M, Weber MM, Pfützner A. Dihydropyrimidine dehydrogenase genotyping and phenotyping for 5-fluorouracil dysmetabolism: moving towards personalized chemotherapy in patients with cancer. Curr Pharmacogenom Pers Med 2009; 7: 27583.
  • 59
    Van Staveren MC, Van Kuilenburg ABP, Visser T, Maring JG. Sensitivity and specificity of an oral uracil loading test in patients with normal DPD activity and with DPD deficiency. Pharm Weekbl 2009; 144: 1836.
  • 60
    Mattison LK, Fourie J, Hirao Y, Koga T, Desmond RA, King JR, Shimizu T, Diasio RB. The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: pharmacokinetic relationship between expired13CO 2 and plasma [2-13C] dihydrouracil. Clin Cancer Res 2006; 12: 54955.
  • 61
    Mattison LK, Ezzeldin H, Carpenter M, Modak A, Johnson MR, Diasio RB. Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test. Clin Cancer Res 2004; 10: 26528.
  • 62
    Goddard AF, Logan RPH. Diagnostic methods for Helicobacter pylori detection and eradication. Br J Clin Pharmacol 2003; 56: 27383.
  • 63
    Thijs JC, Van Zwei AA, Thijs WJ, Oey HB, Karrenbeld A, Stellaard F, Luijt DS, Meyer BC, Kleibeuker JH. Diagnostic tests for Helicobacter pylori: a prospective evaluation of their accuracy, without selecting a single test as the gold standard. Am J Gastroenterol 1996; 91: 21259.
  • 64
    Elwyn G, Taubert M, Davies S, Brown G, Allison M, Phillips C. Which test is best for Helicobacter pylori? A cost-effective model using decision analysis. Br J Gen Pract 2007; 57: 4013.
  • 65
    Braden B, Adams S, Duan L-P, Orth K-H, Maul F-D, Lembcke B, Hor G, Caspary WF. The [13C]acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals. Gastroenterology 1995; 108: 104855.
  • 66
    Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ, Vantrappen G. Measurement of gastric emptying rate of solids by means of a carbon- labelled octanoic acid breath test. Gastroenterology 1993; 104: 16407.
  • 67
    Sikkens ECM, Cahen DL, Kuipers EJ, Bruno MJ. Pancreatic enzyme replacement therapy in chronic pancreatitis. Best Pract Res Clin Gastroenterol 2010; 24: 33747.
  • 68
    Ojetti V, Gigante G, Gabrielli M, Ainora ME, Mannocci A, Lauritano EC, Gasbarrini G, Gasbarrini A. The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: randomized trial. Eur Rev Med Pharmacol Sci 2010; 14: 16370.
  • 69
    Vonk RJ, Stellaard F, Priebe MG, Koetse HA, Hagedoorn RE, De Bruijn S, Elzinga H, Lenoir-Wijnkoop I, Antoine J-M. The 13C/2H-glucose test for determination of small intestinal lactase activity. Eur J Clin Invest 2001; 31: 22633.
  • 70
    Schneider JF, Schoeller DA, Nemchausky B. Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labelled aminopyrine in man. Clin Chim Acta 1978; 84: 15362.
  • 71
    Braden B, Lembcke B, Kuker W, Caspary WF. 13C-breath tests: current state of the art and future directions. Dig Liver Dis 2007; 39: 795805.
  • 72
    van Veen EB. Implementatie van richtlijn 2011/20/EC, Tijdschrift voor Gezondheidsrecht 6 oktober. 2009.
  • 73
    European Commision. Directive 2002/178/EC laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. 2002.
  • 74
    European Commision. Directive 65/65/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products. 1965.
  • 75
    European Commision. Directive 93/42/EEC concerning medical devices. 1993.
  • 76
    European Commision. The rules governing medicinal products in the European Union, Volume 10 – guidance documents applying to clinical trials, questions & answers. Version 7.0, September 2010.
  • 77
    European Commision. The rules governing medicinal products in the European Union, Volume 10 – guidance documents applying to clinical trials, Harmonised requirements for Non Investigational Medicinal products in CTA submissions. June 2010.
  • 78
    European Commision. Directive 2001/20/EC. 4 April 2001.
  • 79
    Heck d'AH, Buttrill Jr, SE, Flynn NW. Bioavailability of imipramine tablets relative to a stable isotope-labelled internal standard: increasing the power of biovailability tests. J Pharmacokinet Biopharm 1979; 7: 23348.
  • 80
    Eichelbaum M, Somogyi A, Von Unruh GE, Dengler HJ. Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil. Eur J Clin Pharmacol 1981; 19: 1337.
  • 81
    Eichelbaum M, Dengler HJ, Somogyi A, Von Unruh GE. Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination. Studies of the relative bioavailability of verapamil tablets. Eur J Clin Pharmacol 1981; 19: 12731.
  • 82
    Meresaar U, Nilsson M-I, Holmstrand J, Anggard E. Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Eur J Clin Pharmacol 1981; 20: 4738.
  • 83
    Rigby GV, Vose CW, Haskins NJ. Propantheline bromide plasma level, urinary excretion and pharmacological data in a comparison of the bioavailability of three oral formulations of Pro-Banthine. Eur J Drug Metab Pharmacokinet 1983; 8: 21924.
  • 84
    Vogelgesang B, Echizen H, Schmidt E, Eichelbaum M. Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of L- and d-verapamil examined with a stable isotope technique. Br J Clin Pharmacol 1984; 18: 73340.
  • 85
    Marvola M, Kannikoski A, Taskinen J, Ottoila P. Assessment of bioavailability of experimental single-unit sustained release tablets of verapamil hydrochloride using the stable isotope technique. J Pharmacy Pharmacol 1985; 37: 76670.
  • 86
    Hatch F, McKellop K, Hansen G, MacGregor T. Relative bioavailability of metaproterenol in humans utilizing a single dose, stable isotope approach. J Pharm Sci 1986; 75: 88690.
  • 87
    Fujioka M, Shinohara Y, Baba S. Acute suppression of endogenous testosterone levels by exogenous testosterone in normal men. Life Sci 1987; 41: 9459.
  • 88
    Looareesuwan S, White NJ, Warrell DA. Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy caucasian volunteers. Br J Clin Pharmacol 1987; 24: 3742.
  • 89
    Mikus G, Fischer C, Heuer B, Langen C, Eichelbaum M. Application of stable isotope methodology to study the pharmacokinetics, bioavailability and metabolism of nitrendipine after i.v. and p.o. administration. Br J Clin Pharmacol 1987; 24: 5619.
  • 90
    Hallen B, Guilbaud O, Stromberg S, Lindeke B. Single-dose pharmacokinetics of terodiline, including a stable isotope technique for improvement of statistical evaluations. Biopharm Drug Dispos 1988; 9: 22950.
  • 91
    Atkinson AJ Jr, Ruo TI, Piergies AA, Breiter HC, Connelly TJ, Sedek GS, Juan D, Hubler GL, Hsieh A-M. Pharmacokinetics of N-acetylprocainamide in patients profiled with a stable isotope method. Clin Pharmacol Ther 1989; 46: 1829.
  • 92
    Fujioka M, Shinohara Y, Baba S, Irie M. Inoue k., Endogenous and exogenous testosterone levels after administration of deuterium-labelled testosterone propionate in hypogonadotropic hypogonadism. Chem Pharm Bull (Tokyo) 1989; 37: 31001.
  • 93
    Shinohara Y, Baba S. Stable isotope methodology in the pharmacokinetic studies of androgenic steriods in humans. Steroids 1990; 55: 1706.
  • 94
    Aronoff G, Brier M, Mayer ML, Barbalas M, Aogaichi K, Sloan R, Brazzell R, Massarella J. Bioavailability and kinetics of cibenzoline in patients with normal and impaired renal function. J Clin Pharmacol 1991; 31: 3844.
  • 95
    Benowitz NL, Jacob P III, Denaro C, Jenkins R. Stable isotope studies of nicotine kinetics and bioavailability. Clin Pharmacol Ther 1991; 49: 2707.
  • 96
    Benowitz NL, Chan K, Denaro CP, Jacob P III. Stable isotope method for studying transdermal drug absorption: the nicotine patch. Clin Pharmacol Ther 1991; 50: 28693.
  • 97
    Bredberg U, Karlsson MO, Borgstrom L. A comparison between the semisimultaneous and the stable isotope techniques for bioavailability estimation of terbutaline in humans. Clin Pharmacol Ther 1992; 52: 23948.
  • 98
    Browne TR, Szabo GK, McEntegart C, Evans JE, Evans BA, Miceli JJ, Quon C, Dougherty CL, Kres J, Davoudi H. Bioavailability studies of drugs with nonlinear pharmacokinetics: II. Absolute bioavailability of intravenous phenytoin prodrug at therapeutic phenytoin serum concentrations determined by double-stable isotope technique. J Clin Pharmacol 1993; 33: 8994.
  • 99
    Hall SD, Rudy AC, Knight PM, Brater DC. Lack of presystemic inversion of (R)- to (S)-ibuprofen in humans. Clin Pharmacol Ther 1993; 53: 393400.
  • 100
    Le Houezec J, Jacob P III, Benowitz NL. A clinical pharmacological study of subcutaneous nicotine. Eur J Clin Pharmacol 1993; 44: 22530.
  • 101
    Richard J, Cardot J-M, Godbillon J. Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations. Eur J Drug Metab Pharmacokinet 1994; 19: 37580.
  • 102
    Hage K, Buhl K, Fischer C, Knebel NG. Estimation of the absolute bioavailability of flecainide using stable isotope technique. Eur J Clin Pharmacol 1995; 48: 515.
  • 103
    Sun JX, Piraino AJ, Morgan JM, Joshi JC, Cipriano A, Chan K, Redalieu E. Comparative pharmacokinetics and bioavailability of nitroglycerin and its metabolites from transderm-nitro, nitrodisc, and Nitro-Dur II systems using a stable-isotope technique. J Clin Pharmacol 1995; 35: 3907.
  • 104
    Voortman G, Paanakker JE. Bioavailability of mirtazapine from Remeron® tablets after single and multiple oral dosing. Hum Psychopharmacol 1995; 10 (Suppl. 2): S8396.
  • 105
    Bode H, Brendel E, Ahr G, Fuhr U, Harder S, Staib AH. Investigation of nifedipine absorption in different regions of the human gastrointestinal (GI) tract after simultaneous administration of 13C- and 12C-nifedipine. Eur J Clin Pharmacol 1996; 50: 195201.
  • 106
    Gross AS, Mikus G, Ratge D, Wisser H, Eichelbaum M. Pharmacokinetics and pharmacodynamics of the enantiomers of gallopamil. J Pharmacol Exp Ther 1997; 281: 110212.
  • 107
    Benech H, Pruvost A, Batel A, Bourguignon M, Thomas J-L, Grognet J-M. Use of the stable isotopes technique to evaluate the bioavailability of a pharmaceutical form of magnesium in man. Pharm Res 1998; 15: 34751.
  • 108
    Fromm MF, Dilger K, Busse D, Kroemer HK, Eichelbaum M, Klotz U. Gut wall metabolism of verapamil in older people: effects of rifampicin-mediated enzyme induction. Br J Clin Pharmacol 1998; 45: 24755.
  • 109
    Dilger K, Eckhardt K, Hofmann U, Kucher K, Mikus G, Eichelbaum M. Chronopharmacology of intravenous and oral modified release verapamil. J Clin Pharmacol 1999; 47: 4139.
  • 110
    Pieniaszek HJ Jr, Mayersohn M, Adams MP, Reinhart RJ, Barrett JS. Moricizine bioavailability via simultaneous, dual, stable isotope administration: bioequivalence implications. J Clin Pharmacol 1999; 39: 81725.
  • 111
    Yeh KC, Stone JA, Carides AD, Rolan P, Woolf E, Ju WD. Simultaneous investigation of indinavir nonlinear pharmacokinetics and bioavailability in healthy volunteers using stable isotope labeling technique: study design and model-independent data analysis. J Pharm Sci 1999; 88: 56873.
  • 112
    Heikkinen H, Saraheimo M, Antila S, Ottoila P, Pentikäinen PJ. Pharmacokinetics of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, in man -A study using a stable isotope technique. Eur J Clin Pharmacol 2001; 56: 8216.
  • 113
    Glaeser H, Drescher S, Hofmann U, Heinkele G, Somogyi AA, Eichelbaum M, Fromm MF. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans. Clin Pharmacol Ther 2004; 76: 2308.
  • 114
    Kasuya Y, Mamada K, Baba S, Matsukura M. Stable-isotope methodology for the bioavailability study of phenytoin during multiple-dosing regimens. J Pharm Sci 1985; 74: 5037.
  • 115
    Foster DJR, Morton EB, Heinkele G, Mürdter TE, Somogyi AA. Stereoselective quantification of methadone and a d6-labelled isotopomer using high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry: application to a pharmacokinetic study in a methadone maintained subject. Ther Drug Monit 2006; 28: 55967.
  • 116
    Majumdar AK, Howard L, Goldberg MR, Hickey L, Constanzer M, Rothenberg PL, Crumley TM, Panebianco D, Bradstreet TE, Bergman AJ, Waldman SA, Greenberg HE, Butler K, Knops A, De Lepeleire I, Michiels N, Petty KJ. Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol 2006; 46: 291300.
  • 117
    Schultz IR, Shangraw RE. Effect of short-term drinking water exposure to dichloroacetate on its pharmacokinetics nd oral bioavailability in human volunteers: a stable isotope study. Toxicol Sci 2006; 92: 4250.