201. A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism
- Author
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N.G.M. Hunfeld, R.H.N. van Schaik, Paul G.H. Mulder, W.P. Geus, E. J. Kuipers, J.C. Kooiman, Daan J Touw, Ron A. A. Mathot, Pharmacy, Clinical Chemistry, Gastroenterology & Hepatology, Nanomedicine & Drug Targeting, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Groningen Research Institute for Asthma and COPD (GRIAC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medicinal Chemistry and Bioanalysis (MCB), Amsterdam institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Other Research
- Subjects
genotype ,Pharmacology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Esomeprazole ,gastric pH monitoring ,human experiment ,esomeprazole ,genetic polymorphism ,Pharmacology (medical) ,education.field_of_study ,Cross-Over Studies ,adult ,Gastroenterology ,Area under the curve ,article ,Gastric Acidity Determination ,Hydrogen-Ion Concentration ,female ,Liver ,priority journal ,Aryl Hydrocarbon Hydroxylases ,medicine.drug ,crossover procedure ,Adolescent ,area under the curve ,Population ,Rabeprazole ,CYP2C19 ,Caucasian ,White People ,rabeprazole ,Gastric Acid ,Young Adult ,Pharmacokinetics ,Double-Blind Method ,male ,medicine ,drug mechanism ,Humans ,heterozygosity ,controlled study ,human ,normal human ,education ,Pantoprazole ,Analysis of Variance ,Polymorphism, Genetic ,Hepatology ,Dose-Response Relationship, Drug ,business.industry ,pH measurement ,Proton Pump Inhibitors ,Models, Theoretical ,Crossover study ,Cytochrome P-450 CYP2C19 ,drug efficacy ,randomized controlled trial ,cytochrome P450 2C19 ,homozygosity ,business - Abstract
Background Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25-30% an intermediate and 2-5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences. Aim To compare the acid-inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics. Methods Eighteen healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*2-*6 and*17 genotype were included in a randomised investigator-blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. Results Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P 4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P
- Published
- 2012