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奥美拉唑在体内对CYP1A2的诱导作用与CYP1A2的基因多态性相关。

Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2.

作者信息

Han Xing-Mei, Ouyang Dong-Sheng, Chen Xiao-Ping, Shu Yan, Jiang Chang-Hong, Tan Zhi-Rong, Zhou Hong-Hao

机构信息

Pharmacogenetics Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan 410078, China.

出版信息

Br J Clin Pharmacol. 2002 Nov;54(5):540-3. doi: 10.1046/j.1365-2125.2002.01686.x.

DOI:10.1046/j.1365-2125.2002.01686.x
PMID:12445035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1874453/
Abstract

AIMS

To evaluate the effect of the CYP1A21C and CYP1A21F 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 CYP1A21F/CYP1A21F and six CYP1A21C/CYP1A21F 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 CYP1A21F/CYP1A21F and CYP1A21C/CYP1A21F 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 CYP1A21F/CYP1A21F and CYP1A21C/CYP1A21F genotypes.

CONCLUSION

The CYP1A21C and CYP1A21F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.

摘要

目的

评估CYP1A21C和CYP1A21F基因多态性对健康受试者中奥美拉唑诱导CYP1A2活性的影响。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法鉴定CYP2C19和CYP1A2的突变。给予12名CYP2C19的广泛代谢者（EM）（其中6名CYP1A21F/CYP1A21F和6名CYP1A21C/CYP1A21F的CYP1A2）每日120 mg奥美拉唑，持续7天。在口服200 mg咖啡因6小时后，分别于第1天、第9天和第16天三次使用咖啡因血浆指数（副黄嘌呤与咖啡因浓度之比）测定CYP1A2活性。

结果

第9天，CYP1A21F/CYP1A21F和CYP1A21C/CYP1A21F基因型的咖啡因比率存在显著差异（P = 0.002），但在第1天或第16天无显著差异（P > 0.05）。CYP1A21F/CYP1A21F和CYP1A21C/CYP1A21F基因型从第9天到第1天（48%±20%对19%±20%）以及从第9天到第16天（50%±31%对15%±22%）比率变化存在显著差异（P < 0.05）。

结论

CYP1A21C和CYP1A21F基因多态性影响奥美拉唑在体内对CYP1A2活性的诱导作用。

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