Change in pharmacokinetics of mycophenolic acid as a function of age in rats and effect of coadministered amoxicillin/clavulanate
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概要
- 論文の詳細を見る
Changes of mycophenolic acid (MPA) pharmacokinetics with aging were investigated in rats. We also compared the effect of concomitant amoxicillin/clavulanate combination (CVA/AMPC) on the pharmacokinetics of MPA in 4-week-old and 12-week-old rats (the package insert of CVA/AMPC warns of possible interaction with MPA). Four-week-old rats showed a 1.4-fold higher total body clearance of MPA and a lower volume of distribution of MPA (65%), compared to the values in 12-week-old rats. However, the difference in MPA pharmacokinetics disappeared when enterohepatic circulation was eliminated by bile duct cannulation (BDC). Concomitant CVA/AMPC significantly reduced plasma MPA concentration in intact rats of both age groups, and the age-dependent difference of MPA pharmacokinetics was no longer apparent. The effect of CVA/AMPC was not seen in rats that had undergone BDC, suggesting that the drug-drug interaction can be attributed to inhibition of enterohepatic circulation by CVA/AMPC. These results indicate that the aging-related alteration of MPA pharmacokinetics is a consequence of immature enterohepatic circulation in 4-week-old rats. Higher doses of MPA may be necessary in juveniles. © 2012 The Pharmaceutical Society of Japan.
著者
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SUGA Yukio
Department of Pharmacy, Kanazawa University Graduate School of Medicine
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Sai Yoshimichi
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Kanazawa University
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Arai Kunizo
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Kanazawa University
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Ishizaki Junko
Department Of Clinical Drug Informatics Faculty Of Pharmaceutical Sciences Kanazawa University
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Ito Satsuki
Department Of Pharmacy Kanazawa University Graduate School Of Medicine
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Miyamoto Ken-ichi
Department Of Applied Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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Miyamoto Ken-ichi
Department of Hospital Pharmacy, Kanazawa University School of Medicine
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Tsuda Tomoko
Department of Clinical Drug Informatics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
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Ito Satsuki
Department of Hospital Pharmacy, Kanazawa University School of Medicine
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Suga Yukio
Department of Clinical Drug Informatics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
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Arai Kunizo
Department of Clinical Drug Informatics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
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