Greenblatt D J, Abernethy D R, Koepke H H, Shader R I
J Clin Pharmacol. 1984 Apr;24(4):187-93. doi: 10.1002/j.1552-4604.1984.tb01829.x.
The influence of cimetidine coadministration, 300 mg every 6 hours, on the kinetics of single oral doses of oxazepam (30 mg), lorazepam (2 mg), and flurazepam (30 mg) was evaluated in healthy volunteers. Cimetidine had no significant effect on the peak plasma concentration or the time of peak concentration for either oxazepam, lorazepam, or desalkylflurazepam (formed from flurazepam). Cimetidine likewise did not alter the elimination half-life of oxazepam (9.4 hours) or lorazepam (11.6 hours), and did not change total AUC for lorazepam. Oxazepam AUC was increased an average of 10 per cent by cimetidine (P less than 0.02). In contrast, cimetidine prolonged desalkylflurazepam elimination half-life (141 vs. 94 hours, P less than 0.1) and increased AUC an average of 65 per cent (P less than 0.05). Thus, cimetidine has little or no influence on the absorption or disposition of oxazepam and lorazepam, two benzodiazepines biotransformed by glucuronide conjugation. However, cimetidine slows the elimination of flurazepam's metabolite, desalkylflurazepam, which is biotransformed by oxidation.
在健康志愿者中评估了每6小时服用300毫克西咪替丁对单次口服奥沙西泮（30毫克）、劳拉西泮（2毫克）和氟西泮（30毫克）动力学的影响。西咪替丁对奥沙西泮、劳拉西泮或去烷基氟西泮（由氟西泮形成）的血浆峰值浓度或峰值浓度出现时间均无显著影响。西咪替丁同样未改变奥沙西泮（9.4小时）或劳拉西泮（11.6小时）的消除半衰期，且未改变劳拉西泮的总AUC。西咪替丁使奥沙西泮的AUC平均增加了10%（P<0.02）。相比之下，西咪替丁延长了去烷基氟西泮的消除半衰期（141小时对94小时，P<0.1），并使AUC平均增加了65%（P<0.05）。因此，西咪替丁对奥沙西泮和劳拉西泮（两种通过葡萄糖醛酸结合进行生物转化的苯二氮䓬类药物）的吸收或处置几乎没有影响。然而，西咪替丁减缓了氟西泮代谢产物去烷基氟西泮的消除，后者通过氧化进行生物转化。
