期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 5, 期 12, 页码 2937-2944出版社
WILEY
DOI: 10.1111/j.1600-6143.2005.01107.x
关键词
cyclosporine; drug-drug interactions; kidney transplantation; mycophenolic acid; pharmacokinetics; sirolimus
The pharmacokinetics of mycophenolic acid (MPA)-the active metabolite of mycophenolate mofetil (MMF)-is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA C-max and T-max were comparable in the two groups, while mean MPA AUC(0-12) was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.
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