PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) OF MYCOPHENOLIC ACID (MPA) IN STABLE RENAL TRANSPLANT RECIPIENTS TREATED WITH SUBOPTIMAL DOSES OF MYCOPHENOLATE MOFETIL (MMF)

794 Suboptimal doses of MMF are frequently employed in renat transplant (Tx) patients with drug-related side effects or low weight. The aim of this study was to compare the MPA PK profile and its PD effect in patients receiving either standard (2g) or low (1.5 or 1g) MMF doses, in order to assess whether low doses of MMF offers therapeutic plasma concentrations of MPA and adequate inhibition of IMPDH activity. Patients and Methods: 23 Tx recipients aged 13 to 55, with a post-Tx follow-up of 38.5±44.8 months (6-166 months) receiving 1g (n=9); 0.75g (n=5) and 0.5g (n=9) of MMF twice a day, in association with cyclosporine and prednisone were included. For MPA exposure, AUC was calculated using pre-dose, 20, 40, 75 minutes and 2, 4, 6, 8 and 12 hours plasma samples. MPA plasma levels were analyzed by HPLC. IMPDH activity was determined at zero, 1, 2 and 4 hours, by the measurement of 3H release from [2,8-3H] hypoxanthine or [2,8-3H] inosine. Results are shown in Tables I and II.Table I: MPA Pharmacokinetics Table II: MPA Pharmacodynamics This results show a high PK and PD interindividual variability, without statistical differences between the three groups. Group 1g showed a more spiked IMPDH inhibition profile, whereas the profile was more flat in groups 2g and 1.5g. In conclusion, therapeutic drug monitoring of MPA could be useful in managing these patients. This research was funded in part by Productos Roche, S.A. (Spain).