Massarella J W, Defeo T M, Liguori J, Passe S, Aogaichi K
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Br J Clin Pharmacol. 1991 Apr;31(4):481-3. doi: 10.1111/j.1365-2125.1991.tb05566.x.
Twelve healthy subjects completed an open single dose study to evaluate the effect of co-administration of cimetidine and ranitidine on the pharmacokinetics of cifenline. Each subject received a single 160 mg dose of cifenline alone, in combination with cimetidine (300 mg four times daily), and with ranitidine (150 mg twice daily). The H2-receptor antagonists were given with breakfast 1 h prior to cifenline dosing and continuing for 48 h. Co-administration of cimetidine significantly increased Cmax (27%) and AUC (44%) and prolonged the half-life (30%) of cifenline. There were no differences in these parameters when ranitidine was co-administered with cifenline. The results of this study suggest that cimetidine, but not ranitidine, lowers the clearance of cifenline by inhibition of hepatic oxidative metabolism.
12名健康受试者完成了一项开放单剂量研究，以评估西咪替丁和雷尼替丁联合给药对西芬利恩药代动力学的影响。每名受试者分别接受单剂量160 mg西芬利恩，以及与西咪替丁（每日4次，每次300 mg）和雷尼替丁（每日2次，每次150 mg）联合给药。H2受体拮抗剂在西芬利恩给药前1小时随早餐服用，并持续48小时。西咪替丁联合给药显著增加了西芬利恩的Cmax（27%）和AUC（44%），并延长了其半衰期（30%）。雷尼替丁与西芬利恩联合给药时，这些参数没有差异。本研究结果表明，西咪替丁而非雷尼替丁通过抑制肝脏氧化代谢降低了西芬利恩的清除率。
