Li G, Klotz U
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Fed. Rep. of Germany.
Arzneimittelforschung. 1990 Oct;40(10):1105-7.
To examine the effect of omeprazole on the hepatic drug metabolizing enzyme system microsomes from rat and human liver samples were incubated with midazolam (CAS 59467-70-8) in the absence and presence of various concentrations of omeprazole (CAS 73590-58-6), its sulfone metabolite and for comparison also with cimetidine. In the extracted incubation mixtures unchanged midazolam, a-OH-midazolam, 4-OH-midazolam and di-OH-midazolam were analyzed by HPLC. In both species omeprazole (and its sulfone) inhibited the formation of all three oxidized metabolites of midazolam and the corresponding IC50-values (range 0.2-1.3 mmol/l for rat microsomes and 0.2-1.5 mmol/l for human microsomes) were comparable to cimetidine (range 0.05 to 3.8 mmol/l). These results indicate that the oxidative metabolism of midazolam can be inhibited in vitro by omeprazole (and/or its sulfone metabolite) and this interaction should be considered if both drugs are administered concomitantly in man.
为研究奥美拉唑对大鼠和人肝脏样本肝药代谢酶系统的影响，在存在和不存在不同浓度奥美拉唑（CAS 73590 - 58 - 6）、其砜代谢物的情况下，将肝脏样本与咪达唑仑（CAS 59467 - 70 - 8）一起孵育，并且为作比较还与西咪替丁一起孵育。在提取的孵育混合物中，通过高效液相色谱法分析未变化的咪达唑仑、α-羟基咪达唑仑、4 - 羟基咪达唑仑和二羟基咪达唑仑。在这两个物种中，奥美拉唑（及其砜）均抑制咪达唑仑所有三种氧化代谢物的形成，并且相应的IC50值（大鼠微粒体范围为0.2 - 1.3 mmol/L，人微粒体范围为0.2 - 1.5 mmol/L）与西咪替丁（范围为0.05至3.8 mmol/L）相当。这些结果表明，奥美拉唑（和/或其砜代谢物）在体外可抑制咪达唑仑的氧化代谢，并且如果在人体中同时给予这两种药物，应考虑这种相互作用。
