Effects of Calcineurin Inhibitors on Pharmacokinetics of Mycophenolic Acid and Its Glucuronide Metabolite during the Maintenance Period Following Renal Transplantation(Pharmacology)
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概要
- 論文の詳細を見る
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 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.
- 公益社団法人日本薬学会の論文
- 2006-02-01
著者
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SUZUKI Kazuo
Department of Immunology, Inflammatory Program, Chiba University School of Medicine
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KAGAWA Yoshiyuki
Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University
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Ushiyama Tomomi
Department Of Surgery Kikugawa General Hospital
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OZONO Seiichiro
Department of Urology, Nara Medical University
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MAEDA TOSHIO
Department of Pharmacology, The Research Institute of Applied Sciences for Traditional Chinese Medic
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Naito T
浜松医科大学 医学部附属病院薬剤部
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Naito Takafumi
Department Of Hospital Pharmacy Hamamatsu University School Of Medicine
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Suzuki Kazuo
Department Of Urology Hamamatsu University School Of Medicine
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OTSUKA Atsushi
Department of Urology, Hamamatsu University School of Medicine
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TAKAYAMA Tatsuya
Department of Urology, Hamamatsu University School of Medicine
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NAITO Takafumi
Division of Hospital Pharmacy, Hamamatsu University School of Medicine
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SHINNO Kazuko
Division of Hospital Pharmacy, Hamamatsu University School of Medicine
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HASHIMOTO Hisakuni
Division of Hospital Pharmacy, Hamamatsu University School of Medicine
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Naito Takafumi
Division Of Hospital Pharmacy Hamamatsu University School Of Medicine
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Kagawa Yoshiyuki
Department Of Pharmacokinetics And Pharmacodynamics And Global Center Of Excellence (coe) And Clinic
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Kagawa Yoshiyuki
Department Of Clinical Pharmaceutics And Pharmacy Practice Faculty Of Pharmaceutical Sciences Univer
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Shinno Kazuko
Department Of Urology Hamamatsu University School Of Medicine
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Ozono Seichro
Department Of Urology Hamamatsu University School Of Medicine
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Otsuka Atsushi
Department Of Dermatology Shimane Prefectural Central Hospital
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Suzuki Kazuo
Department Of Hamamatsu University School Of Medicine
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Ushiyama Tomomi
Department Of Hamamatsu University School Of Medicine
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Ozono Seiichiro
Department Of Hamamatsu University School Of Medicine
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Takayama Tatsuya
Department Of Hamamatsu University School Of Medicine
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Hashimoto Hisakuni
Division Of Hospital Pharmacy Hamamatsu University School Of Medicine
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Kagawa Yoshiyuki
Department Of Pharmacokinetics And Pharmacodynamics Global Center Of Excellence (coe) And Clinical P
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Maeda Toshio
Department Of Clinical Pharmaceutics Faculty Of Pharmaceutical Sciences University Of Shizuoka
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Uehara Takashi
Second Department Of Surgery Hamamatsu University School Of Medicine
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Otsuka Atsushi
浜松医科大学 泌尿器科学
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Suzuki Kazuo
Departmens Of Oral Histology Matsumoto Dental College
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Otsuka Atsushi
Department Of Dermatology Kyoto University
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Kagawa Yoshiyuki
Department of Clinical Pharmaceutics & Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Maeda Toshio
Department of Clinical Pharmaceutics & Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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