Han Xing-Mei, Ouyang Dong-Sheng, Chen Xiao-Ping, Shu Yan, Jiang Chang-Hong, Tan Zhi-Rong, Zhou Hong-Hao
Pharmacogenetics Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan 410078, China.
Br J Clin Pharmacol. 2002 Nov;54(5):540-3. doi: 10.1046/j.1365-2125.2002.01686.x.
To evaluate the effect of the CYP1A21C and CYP1A21F polymorphisms on the inducibility of CYP1A2 by omeprazole in healthy subjects.
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.
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.
The CYP1A21C and CYP1A21F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.
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。
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。
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)。
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。