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.

OKT3 monitoring in the treatment of steroid-resistant acute rejection of hepatotransplant recipients.

OKT3 is a monoclonal antibody used as T-specific immunosuppressor agent in the treatment of acute rejection of hepato- or renal-transplanted patients. The immunosuppressor effect is related to the elimination and modulation of T-cells after the binding between OKT3 and the specific antigen CD3+. This drug has been used in the treatment of acute rejection. The more frequent side effects is the immunogenic reaction Human Antibody Mouse Antibody (HAMA). The aim of this study is the evaluation of the dose and the administration route of the OKT3. The results of the antibody monitoring in the plasma of the treated patients and the analysis of the clinical data were evaluated to focus a valid therapeutic protocol as well as a more rational time sampling of the circulating drug to achieve a correct monitoring. The results show a gradual increase of the hematic concentration of the drug, positively correlating the clinical data of hepatic biopsy and lymphocytic screening. These results have permitted to modify the therapeutic protocol previously performed. It has been defined the administration route choosing i.v. infusion (5 mg/die/2 h), moreover it the therapy has been shortened to 6 days. The HAMA were also evaluated and the analysis of the data showed a negative results, suggesting the possibility of the OKT3 retreatment in the cases of rescue.