Journal
BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volume 29, Issue 2, Pages 275-280Publisher
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.29.275
Keywords
mycophenolic acid; calcineurin inhibitor; renal transplantation; maintenance period; therapeutic drug monitoring; individual variability
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Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF) has been introduced into renal transplant immunosuppressant protocols in combination with calcineurin inhibitors (CNIs) and steroids. This study compared the pharmacokinetic profiles of MPA and its major metabolite MPA glucuronide (MPAG) in combination with tacrolimus (TAC) or cyclosporine (CyA) during the maintenance period (> 6 months) following renal transplantation. There was no difference between TAC and CyA-treated groups in MPA plasma concentration before drug administration (C-0). MPA C-0, in TAC and CyA-treated patients did not differ from that in patients who were not treated with a CNI. In patients treated with a CNI, MPAG C-0, was significantly greater in those treated with CyA compared with TAC. The MPAG/MPA ratio in CyA-treated patients was significantly greater than that in the TAC-treated group. We observed that C-0 of MPA was negatively correlated with that of TAC and CyA. Positive correlation between MPA C-0, MPAG C-0 and serum creatinine was stronger in patients treated with CyA compared with TAC. Our study suggests that CyA, but not TAC, inhibits enterohepatic circulation of MPAG as a secondary excretion pathway, and that renal function makes a major contribution to elimination of MPA and MPAG. We indicate that it may he necessary to estimate biliary excretion of MPAG to avoid the risk of intestinal injury in patients receiving combination therapy with TAC during the maintenance period.
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