The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects.
BACKGROUND
Lansoprazole is a gastric proton-pump inhibitor and has been demonstrated to be effective in the treatment of various peptic diseases. The effects of CYP2C19 activity on the pharmacokinetics of lansoprazole and its active metabolites in Chinese subjects have not previously been evaluated.


OBJECTIVE
The study aimed to evaluate the effects of CYP2C19 activity in healthy Chinese volunteers.


METHODS
Twenty-two healthy volunteers were recruited for an open trial and received a single dose of 30 mg lansoprazole. Using a validated LC-MS/MS method, we measured the plasma concentrations of lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone. The genotype of CYP2C19 was identified by polymerase chain reaction (PCR) analysis of single nucleotide polymorphisms (SNPs). Subjects were genotypically classified into the following three groups on the basis of PCR-SNP analysis for CYP2C19: homozygous EM (hmEM) group, heterozygous EM (htEM) group, and PM group. To test differences in pharmacokinetic parameters among the three groups, analysis of variance (ANOVA) after log-transformation of data was used.


CONCLUSIONS
Our results indicated that there were significant differences (p < 0.001) between the hmEM and PM groups, between the htEM and PM groups, and between the hmEM and htEM groups in C(max), AUC(0-t), and AUC(0-inf) of lansoprazole and lansoprazole sulfone. There were also significant differences (p < 0.001) between the hmEM and PM groups, and between the htEM and PM groups in C(max) of 5-hydroxylansoprazole.
Xu
Hong-Rong
HR
Department of Clinical Pharmacology, ZhongShan Hospital, Fudan University, Shanghai, China. xu.hongrong@zs-hospital.sh.cn
Chen
Wei-Li
WL
Li
Xue-Ning
XN
Chu
Nan-Nan
NN
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D064747:Lansoprazole; D008297:Male; D054328:Proton Pump Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; C581535:Lansoprazole Sulfone; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19