EFFECTS OF CARBAMAZEPINE ON CYCLOSPORINE METABOLISM IN PEDIATRIC RENAL-TRANSPLANT RECIPIENTS

This study documents a pharmacokinetic interaction between carbamazepi ne and cyclosporine (CsA) in pediatric renal transplant recipients. No ncompartmental. steady-state CsA pharmacokinetics were determined in t hree pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long-term therapy (carbamazepine group) and in t hree matched renal. transplant subjects who were not receiving carbama zepine (control group). Even though the mean daily dosage of CsA was c onsistently higher in the carbamazepine group than in the control grou p (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 carbam azepine group (57 ng/ml vs 162 ng/ml, respectively; p=0.0023). Mean av erage steady-state blood concentrations of CsA (C-av) per mg of CsA ad ministered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic m etabolism or a reduced systemic bioavailability (possible induction of pre-hepatic metabolism) by concurrent use of carbamazepine.