D'Souza M J, Pollock S H, Solomon H M
Department of Pharmaceutical Sciences, School of Pharmacy, Mercer University, Atlanta, GA 30312.
Drug Metab Dispos. 1988 Jan-Feb;16(1):57-9.
Cyclosporine (CsA) is used to prevent rejection of transplanted organs. It is extensively metabolized in the liver by the mixed function oxidase enzyme system by demethylation and hydroxylation. Since cimetidine is a widely prescribed H2 antagonist drug which is known to inhibit the P-450 enzyme system, we studied the effect of chronic treatment with cimetidine on CsA by determining the disposition of CsA (15 mg/kg, iv), prior to and after chronic treatment with cimetidine (60 mg/kg, po), for 5 days. CsA was determined by an HPLC procedure. The clearance (Cl) of CsA was significantly reduced following treatment with cimetidine when compared to the Cl value obtained in the control group (15.46 versus 10.36 ml/min/kg). There were no significant changes in the volume of distribution of CsA, one reason being that cimetidine and cyclosporine bind to different proteins. From the results obtained, we conclude that since cimetidine is an inhibitor of the mixed function oxidase system enzyme system, it inhibits the metabolism of CsA.
环孢素（CsA）用于预防移植器官的排斥反应。它在肝脏中通过混合功能氧化酶系统进行广泛代谢，代谢方式为去甲基化和羟基化。由于西咪替丁是一种广泛使用的H2拮抗剂药物，已知其能抑制P - 450酶系统，我们通过测定在西咪替丁（60 mg/kg，口服）慢性治疗5天前后静脉注射15 mg/kg CsA的处置情况，研究了西咪替丁慢性治疗对CsA的影响。CsA通过高效液相色谱法测定。与对照组获得的清除率（Cl）值相比，西咪替丁治疗后CsA的清除率显著降低（分别为15.46与10.36 ml/min/kg）。CsA的分布容积没有显著变化，原因之一是西咪替丁和环孢素与不同的蛋白质结合。从获得的结果来看，我们得出结论，由于西咪替丁是混合功能氧化酶系统的抑制剂，它抑制了CsA的代谢。
