Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.
OBJECTIVE
To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach.


METHODS
Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition.


RESULTS
The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease.


CONCLUSIONS
The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.
Sheng
Yu-Cheng
YC
Center for Drug Clinical Research, Shanghai University of Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China. shengyc@gmail.com
Wang
Kun
K
He
Ying-Chun
YC
Yang
Juan
J
Zheng
Qing-Shan
QS
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005745:Gastric Acidity Determination; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D064750:Rabeprazole; D013997:Time Factors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19