Cyclosporine-phenytoin interaction.

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.