The effect of chronic administration of cyclosporin A on phenytoin pharmacokinetic parameters in the rat.

The potential for a drug interaction between cyclosporin A and phenytoin was investigated in rats. Rats were treated daily for 14 days with cyclosporin A (50 mg/Kg, s.c.) and on the day of the experiment phenytoin (10 mg/Kg) was administered intravenously. The mean residence time, the elimination half-life and the volume of distribution at steady state were significantly higher in the cyclosporin A-treated group than in the control group. However, total body clearance was similar in both groups. Plasma levels of urea, aspartate aminotransferase (AST) and glucose were significantly higher in the cyclosporin A-treated group than the control group. It was concluded that the observed changes could have been, at least in part, due to an inhibitory effect of cyclosporin A on liver drug metabolizing enzymes and/or liver and kidney damage.