Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans

World J Gastroenterol. 2006 Aug 7;12(29):4750-3. doi: 10.3748/wjg.v12.i29.4750.

Abstract

Aim: To observe the pharmacokinetics and pharmaco-dynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups.

Methods: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography.

Results: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole.

Conclusion: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.

Publication types

  • Clinical Trial

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Adult
  • Anti-Ulcer Agents / pharmacokinetics*
  • Anti-Ulcer Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian Continental Ancestry Group / genetics*
  • Benzimidazoles / pharmacokinetics*
  • Benzimidazoles / pharmacology*
  • China
  • Cytochrome P-450 CYP2C19
  • Dose-Response Relationship, Drug
  • Gastrins / blood*
  • Genotype
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Metabolism / genetics
  • Mixed Function Oxygenases / genetics*
  • Omeprazole / analogs & derivatives*
  • Omeprazole / pharmacokinetics
  • Omeprazole / pharmacology
  • Polymorphism, Restriction Fragment Length
  • Rabeprazole
  • Stomach / physiology

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Benzimidazoles
  • Gastrins
  • Rabeprazole
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole