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标题：Effects of Calcineurin Inhibitors on Pharmacokinetics of Mycophenolic Acid and Its Glucuronide Metabolite during the Maintenance Period Following Renal Transplantation
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作者：Takafumi Naito ; Kazuko Shinno ; Toshio Maeda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：2
页码：275-280
DOI：10.1248/bpb.29.275
出版社：The Pharmaceutical Society of Japan
摘要：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 (C₀). MPA C₀ 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 C₀ 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 C₀ of MPA was negatively correlated with that of TAC and CyA. Positive correlation between MPA C₀, MPAG C₀ 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 be 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.
关键词：mycophenolic acid;calcineurin inhibitor;renal transplantation;maintenance period;therapeutic drug monitoring;individual variability