Inducibility of CYP1A2 by orneprazole in vivo related to the genetic polymorphism of CYP1A2

被引：74

作者：

Han, XM ^{[1
]}

Ouyang, DS ^{[1
]}

Chen, XP ^{[1
]}

Shu, Y ^{[1
]}

Jiang, CH ^{[1
]}

Tan, ZR ^{[1
]}

Zhou, HH ^{[1
]}

机构：

[1] Cent S Univ, Xiang Ya Sch Med, Pharmacogenet Res Inst, Changsha 410078, Hunan, Peoples R China

来源：

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2002年 / 54卷 / 05期

关键词：

caffeine; CYP1A2; genetic polymorphism; induction;

D O I：

10.1046/j.1365-2125.2002.01686.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aims To evaluate the effect of the CYP1A2*1C and CYP1A2*1F polymorphisms on the inducibility of CYP1A2 by omeprazole in healthy subjects. Methods Mutations of CYP2C19 and CYP1A2 were identified by PCR-RFLP. Omeprazole, 120 mg day(-1), was given to 12 extensive metabolizers (EM) with respect to CYP2C19 (six CYP1A2*1F/CYP1A2*1F and six CYP1A2*1C/CYP1A2*1F of CYP1A2) for 7 days. CYP1A2 activity was determined on three occasions, namely on day 1, day 9 and day 16 using the caffeine plasma index (the ratio of the concentrations of paraxanthine to caffeine), 6 h after oral administration of 200 mg caffeine. Results There was a significant difference (P = 0.002) between the caffeine ratios for CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes on day 9, but not on day 1 or day 16 (P > 0.05). The changes in the ratios from day 9 to day 1 (48% +/- 20% vs 19% +/- 20%) and from day 9 to day 16 (50% +/- 31% vs 15% +/- 22%) were significantly different (P < 0.05) between the CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes. Conclusion The CYP1A2*1C and CYP1A2*1F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.

引用

页码：540 / 543

页数：4

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