Pharmacokinetic monitoring of mycophenolate mofetil in kidney transplantedpatients

Mycophenolate mofetil (MMF) is a new immunosuppressant drug used in associa tion with cyclosporin and oral corticosteroids to prevent acute rejection f ollowing renal allograft transplantation. MMF is an ester pro-drug of mycop henolic acid (MFA), the true active species, into which it is completely tr ansformed after oral administration. The recommended initial dose to preven t kidney transplant rejection is 2 g/day irrespective of body weight, 1 g t wice daily. The goal of this study was to correlate dosage (fixed or by bod y weight) and toxic effects to some non-compartmental values such as peak l evel (C-max), time to peak level (T-max) and trough level (C-min). In a sma ll number of patients who had already reached the plasma steady state, we f ound a large inter-patient variability, while the same qualitative pharmaco kinetic profile (as T-max) was conserved. At plasma trough level > 4 mu g/m l some serious toxic effects were observed, whereas at C-min < 2 mu g/ml, t here were some cases of interstitial rejection. There was also a negative c orrelation between dosage and body weight, suggesting that dosages related to body weight might be better than fixed ones. Finally, monitoring plasma level of drug from transplantation to at least 12 months after surgery, at fixed MFA dosage, a small but significant decline of MFA plasma levels was found. (C) 2000 Elsevier Science S.A. All rights reserved.