Effects of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of omeprazole in Chinese people

被引:33
作者
Hu, Xiang-Peng
Xu, Jian-Ming [1 ]
Hu, Yong-Mei
Mei, Qiao
Xu, Xin-Hua
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Hefei, Peoples R China
[2] Affiliated Hosp 1, Wenzhou Med Coll, Ctr Endoscop Diagnos & Therapy, Hefei, Peoples R China
关键词
CYP2C19; genetic polymorphism; omeprazole; pharmacodynamics; pharmacokinetics;
D O I
10.1111/j.1365-2710.2007.00851.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: To investigate whether the pharmacodynamics and pharmacokinetics of omeprazole (OPZ) are dependent of the CYP2C19 genotype status in Chinese people. Methods: Eighteen healthy subjects were voluntary to participate in the study, whose CYP2C19 genotype status were determined by polymerase chain reaction-restriction fragment length polymorphism method. There were six homozygous extensive metabolizers, six heterozygous extensive metabolizers and six poor metabolizers (PMs). All subjects were Helicobacter pylori-negative, determined by serology method and C-13-urea breath test. After d1 and d8 orally received OPZ 20 mg once daily in the morning, intragastric pH values were monitored for 24 h by Digitrapper pH. Meanwhile, blood samples were collected at various time-points until 24 h after administration. The serum concentrations of OPZ were measured by liquid chromatography. Results: After single or repeated doses, the PMs showed a significantly higher mean area under the serum concentration-time curves (AUC) values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers, with a relative ratio of 1.0 : 1.1 : 4.2 and 1.0 : 1.3 : 3.3 (homozygous extensive metabolizers:heterozygous extensive metabolizers:poor metabolizers), respectively. After a single dose of OPZ, significant differences in intragastric pH median, pH > 3 holding time and pH > 4 holding time were observed among the three groups. After repeated doses, the PMs showed a significantly higher intragastric pH values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers. Conclusion: The pharmacodynamic effects of OPZ and its pharmacokinetics depend on the CYP2C19 genotype status in Chinese people.
引用
收藏
页码:517 / 524
页数:8
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