Pharmacokinetic monitoring of mycophenolate mofetil in kidney transplanted patients.
Mycophenolate mofetil (MMF) is a new immunosuppressant drug used in association with cyclosporin and oral corticosteroids to prevent acute rejection following renal allograft transplantation. MMF is an ester pro-drug of mycophenolic acid (MFA), the true active species, into which it is completely transformed after oral administration. The recommended initial dose to prevent kidney transplant rejection is 2 g/day irrespective of body weight, 1 g twice daily. The goal of this study was to correlate dosage (fixed or by body weight) and toxic effects to some non-compartmental values such as peak level (Cmax), time to peak level (Tmax) and trough level (Cmin). In a small number of patients who had already reached the plasma steady state, we found a large inter-patient variability, while the same qualitative pharmacokinetic profile (as Tmax) was conserved. At plasma trough level > 4 microg/ml some serious toxic effects were observed, whereas at Cmin < 2 microg/ml, there were some cases of interstitial rejection. There was also a negative correlation 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.
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Scuola di Specializzazione in Farmacia Ospedaliera, Dipartimento di Scienza e Tecnologia del Farmaco dell'Università di Torino, Turin, Italy.
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D000284:Administration, Oral; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D007166:Immunosuppressive Agents; D011355:Prodrugs; D009173:Mycophenolic Acid