D'Souza M J, Pollock S H, Solomon H M
Dept. of Pharmaceutical Sciences, School of Pharmacy, Mercer University, Atlanta, GA 30312.
Drug Metab Dispos. 1988 Mar-Apr;16(2):256-8.
Cyclosporine (CsA), an immunosuppressant, is used widely to prevent rejection of transplanted organs. It is extensively metabolized in the liver by hydroxylation and demethylation. Since phenytoin is used extensively post-transplant as an anti-convulsant, we studied the effect of chronic treatment with phenytoin on CsA by determining the disposition of CsA, prior to and after chronic treatment with phenytoin (30 mg/kg, po) for 5 days. CsA was analyzed by HPLC. The clearance (CL) of CsA was significantly enhanced following treatment with phenytoin when compared to the CL values obtained pretreatment (15.46 +/- 0.76 vs. 25.3 +/- 3.11 ml/min/kg). There were no significant changes in the volume of distribution of CsA. From the above data, we conclude that phenytoin probably induces the metabolism of CsA.
环孢素（CsA）作为一种免疫抑制剂，被广泛用于预防移植器官的排斥反应。它在肝脏中通过羟基化和去甲基化进行广泛代谢。由于苯妥英在移植后被广泛用作抗惊厥药，我们通过测定苯妥英（30mg/kg，口服）慢性治疗5天前后环孢素的处置情况，研究了苯妥英慢性治疗对环孢素的影响。环孢素通过高效液相色谱法进行分析。与治疗前获得的清除率（CL）值相比，苯妥英治疗后环孢素的清除率显著提高（15.46±0.76对25.3±3.11ml/min/kg）。环孢素的分布容积没有显著变化。根据上述数据，我们得出结论，苯妥英可能诱导环孢素的代谢。
