Effects of carbamazepine on cyclosporine metabolism in pediatric renal transplant recipients.

This study documents a pharmacokinetic interaction between carbamazepine and cyclosporine (CsA) in pediatric renal transplant recipients. Noncompartmental steady-state CsA pharmacokinetics were determined in three pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long-term therapy (carbamazepine group) and in three matched renal transplant subjects who were not receiving carbamazepine (control group). Even though the mean daily dosage of CsA was consistently higher in the carbamazepine group than in the control group (16.2 mg/kg/24 hrs vs 10.8 mg/kg/24 hrs, respectively), the predose trough CsA blood concentrations were significantly lower in the carbamazepine group (57 ng/ml vs 162 ng/ml, respectively; p = 0.0023). Mean average steady-state blood concentrations of CsA (Cav) per mg of CsA administered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic metabolism or a reduced systemic bioavailability (possible induction of pre-hepatic metabolism) by concurrent use of carbamazepine.