Ruffalo R L, Thompson J F, Segal J L
South Med J. 1981 Sep;74(9):1075-8. doi: 10.1097/00007611-198109000-00016.
Cimetidine has been shown to inhibit the liver microsomal metabolism of the benzodiazepines diazepam and chlordiazepoxide, resulting in an increase in half-life and decrease in the clearance of these two drugs. Patients receiving the combination of diazepam and cimetidine have been noted to be more sedated than when given an equal dose of diazepam alone. Many benzodiazepines undergo N-dealkylation and hydroxylation via the cytochrome P450 oxidase system. Cimetidine is thought to bind to cytochrome P450 oxidase and to interfere with many drugs using this path way. Oxazepam and lorazepam are two benzodiazepines not oxidatively metabolized by cytochrome P450, but are glucuronidated by glucuronyl transferase and are, therefore, not subject to metabolic inhibition by cimetidine. Thus, when clinically indicated, oxazepam and lorazepam may be the benzodiazepines of choice to use in combination with cimetidine to eliminate the clinically significant drug interaction seen with diazepam and chlordiazepoxide.
西咪替丁已被证明可抑制苯二氮䓬类药物地西泮和氯氮䓬的肝脏微粒体代谢，导致这两种药物的半衰期延长和清除率降低。据观察，接受地西泮和西咪替丁联合用药的患者比单独给予等量地西泮时更易出现镇静作用。许多苯二氮䓬类药物通过细胞色素P450氧化酶系统进行N-脱烷基化和羟基化反应。西咪替丁被认为可与细胞色素P450氧化酶结合，并干扰许多通过此途径代谢的药物。奥沙西泮和劳拉西泮是两种不通过细胞色素P450进行氧化代谢的苯二氮䓬类药物，而是通过葡萄糖醛酸转移酶进行葡萄糖醛酸化，因此不受西咪替丁的代谢抑制作用影响。因此，在临床有指征时，奥沙西泮和劳拉西泮可能是与西咪替丁联合使用的首选苯二氮䓬类药物，以消除与地西泮和氯氮䓬相关的具有临床意义的药物相互作用。
