Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype.
OBJECTIVE
Omeprazole, lansoprazole and rabeprazole have been widely used as proton pump inhibitors (PPIs). They can be metabolized in the liver by CYP2C19, a polymorphic enzyme, and have a wide inter-individual variability with respect to drug response. In the investigation reported here, we examined the kinetic characteristics of the three PPIs in healthy Chinese subjects in relation to CYP2C19 genotype status.


METHODS
Six homozygous extensive metabolizers (homEMs), six heterozygous extensive metabolizers (hetEMs) and six poor metabolizers (PMs) were recruited for the study from a total of 90 healthy Chinese volunteers whose CYP2C19 genotype status was determined by means of PCR-restriction fragment length polymorphism (RFLP). The study was had an open label, randomized, three-way crossover design. After a single oral dose of 40 mg omeprazole, 30 mg lansoprazole or 40 mg rabeprazole, plasma concentrations of the three PPIs were determined by HPLC.


RESULTS
There were some differences for the area under the plasma concentration-time curve (AUC), the elimination half-life (t(1/2 ke)) and the maximum plasma concentration (c(max)) in the three groups. In the homEMs, hetEMs and PMs, the relative AUC(0-infinity) values were 1:2.8:7.5 for omeprazole, 1:1.7:4.0 for lansoprazole and 1:1.6:3.7 for rabeprazole, respectively; the relative t(1/2 ke) values were 1:1.02:1.65 for omeprazole, 1:1.08:2.39 for lansoprazole and 1:1.37:1.85 for rabeprazole, respectively; the relative c(max) values were 1:2.09:4.39 for omeprazole, 1:1.34:1.72 for lansoprazole, and 1:1.24:2.04 for rabeprazole, respectively.


CONCLUSIONS
The pharmacokinetic characteristics of the three PPIs are significantly dependent on the CYP2C19 genotype status. These data indicate that individualized dose regimen of the three PPIs, based on identification of genotype, can be of great benefit for ensuring the reasonable use of these drugs.
Qiao
Hai-Ling
HL
Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, 450052, People's Republic of China. qiaohl@zzu.edu.cn
Hu
Yu-Rong
YR
Tian
Xin
X
Jia
Lin-Jing
LJ
Gao
Na
N
Zhang
Li-Rong
LR
Guo
Yu-Zhong
YZ
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002681:China; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000097:blood / Q000493:pharmacokinetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D054328:Proton Pump Inhibitors; D064750:Rabeprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole