Pharmacokinetics of lansoprazole in Chinese healthy subjects in relation to CYP2C19 genotypes.
OBJECTIVE
To study the kinetic characteristics of lansoprazole in healthy Chinese subjects in relation to CYP2C19 genotype status for the individualized dose regimen of lansoprazole.


METHODS
Nine homozygous extensive metabolizers (homo EMs) and 9 poor metabolizers (PMs) were recruited for the study from a total of 70 healthy Chinese volunteers, whose CYP2C19 genotype status was determined by the PCR-RFLP techniques. After a single oral dose of 30 mg lansoprazole capsule, plasma concentrations of lansoprazole were determined with HPLC method.


RESULTS
In Chinese subjects, the allele frequencies of the CYP2C19m1 and CYP2C19m2 mutation were 0.35 and 0.07, respectively. The concentration-time curves in the two groups were best fitted to a one-compartment model. In the homo EMs and the PMs groups, the main kinetic parameters were as follows: Tmax (2.44+/-0.85) and (2.33+/-0.94) h, Cmax(1.10+/-0.34) and (1.73+/-0.56) mg/L, Cl/F (16.55+/-0.38) and (3.58+/-1) L/h, T1/2ke (1.96+/-0.51) and (4.21+/-0.53) h, AUC were (3.23+/-0.08) and (11.05+/-0.23) mg.L(-1). A significant difference in AUC, T1/2ke, Cl/F, Cmax values existed between the two groups (P<0.01).


CONCLUSIONS
CYP2C19 genotype is the major factor to influence the interindividual kinetic variability of lansoprazole. Individualized dose regimen of lansoprazole, based on identification of genotype, can be of great benefit for the reasonable use of this drug.
Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou 450052, China.
Yu-Rong
YR
Hu
Hai-Ling
HL
Qiao
Quan-Cheng
QC
Kan
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D002681:China; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole