Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC-MPS) co-administered with cyclosporine in the early-phase post-kidney transplantation.

Mycophenolate drug levels are decreased by co-administration of cyclosporine. However, mycophenolate levels may be associated with insufficient immunosuppression. We investigated the pharmacokinetics of 720 mg mycophenolate sodium (EC-MPS) and inosine monophosphate dehydrogenase (IMPDH) activity under co-medication with cyclosporine and steroids within the first 30 d after kidney transplantation (n = 24). Blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h after the morning dose. Plasma concentrations of mycophenolic acid, its glucuronide metabolites (MPAG; AcMPAG), and free MPA were determined using validated HPLC-DAD. IMPDH activity in leukocytes was analyzed chromatographically. Only six of 24 patients had an MPA-AUC(12h) within the putative therapeutic range of 40-60 mg/L·h. MPA clearance was high with 29 L/h. fMPA-AUC(12h) (r = -0.429, p = 0.04) and MPAG-AUC(12h) correlated significantly with the glomerular filtration rate, while total MPA did not. The MPAG-AUC(12h) was about 52-fold higher than the corresponding values for MPA, whereas the AcMPAG-AUC(12h) reached about 20.4% of the respective MPA-AUC(12h.) We found significant correlations between IMPDH inhibition and MPA concentration (r = -0.665; p < 0.0001), fMPA (r = -0.446; p = 0.003), and AcMPAG (r = -0.459; p = 0.002) but not with MPAG. Only 25% of the patients attained the therapeutic range for MPA-AUC under standard EC-MPS dose during the early-phase post-transplantation. We recommend that EC-MPS should be given in higher doses (3 × 720 mg) in the early post-transplant period when co-administered with cyclosporine.