Nousbaum J B, Berthou F, Carlhant D, Riche C, Robaszkiewicz M, Gouerou H
Service d'Hépato-gastroentérologie, Centre Régional de Pharmacovigilance, CHRU Morvan, Brest, France.
Am J Gastroenterol. 1994 Mar;89(3):371-5.
It has been suggested that omeprazole is an inducer of the cytochrome P450 1A, both in vitro and in vivo. To evaluate whether omeprazole treatment might affect the activity of P450 1A2, we performed a study of caffeine metabolism, which is mainly via P450 1A.
Thirteen subjects (one healthy volunteer and 12 patients) who were treated with omeprazole, 20 mg each morning for 4 wk, and a control group of 13 healthy volunteers, participated in the study. A test of caffeine metabolism was performed before treatment, 28 days after beginning treatment and, whenever possible, 28 days after treatment. Blood samples were analyzed for theobromine, paraxanthine, and theophylline, by high performance liquid chromatography.
P4501A2 activity was determined as the ratio of (paraxanthine + theobromine + theophylline)/(metabolites + caffeine) which represents the total caffeine N-oxidative demethylations; this ratio was expressed as a percentage. For patients, on day 0, the percentage of total metabolism was 34.3% +/- 8.3; on day 28, it was 42.7% +/- 10.8; the difference was statistically significant (p < 0.01). No intra-individual variation of P450 1A2 activity was observed in the control group.
These results demonstrate that omeprazole increases the metabolism of caffeine, especially N-1 and N-3 demethylation pathways, after 28 days of treatment with omeprazole, and suggest that omeprazole, when used for this period, is an inducer of hepatic cytochrome P4501A2.
已有研究表明，奥美拉唑在体外和体内均为细胞色素P450 1A的诱导剂。为评估奥美拉唑治疗是否会影响P450 1A2的活性，我们开展了一项关于咖啡因代谢的研究，咖啡因主要通过P450 1A进行代谢。
13名受试者（1名健康志愿者和12名患者）参与了本研究，这些受试者每天早晨服用20 mg奥美拉唑，持续4周，另有13名健康志愿者作为对照组。在治疗前、开始治疗28天后以及尽可能在治疗结束28天后进行咖啡因代谢测试。通过高效液相色谱法分析血样中的可可碱、副黄嘌呤和茶碱。
P4501A2活性通过（副黄嘌呤 + 可可碱 + 茶碱）/（代谢物 + 咖啡因）的比值来确定，该比值代表总的咖啡因N-氧化去甲基化；此比值以百分比表示。对于患者，在第0天，总代谢百分比为34.3%±8.3；在第28天，为42.7%±10.8；差异具有统计学意义（p < 0.01）。对照组未观察到P450 1A2活性的个体内变化。
这些结果表明，奥美拉唑治疗28天后可增加咖啡因的代谢，尤其是N-1和N-3去甲基化途径，并提示在此期间使用奥美拉唑时，它是肝细胞色素P4501A2的诱导剂。
