2012年7月
Change in Pharmacokinetics of Mycophenolic Acid as a Function of Age in Rats and Effect of Coadministered Amoxicillin/Clavulanate
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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- 巻
- 35
- 号
- 7
- 開始ページ
- 1009
- 終了ページ
- 1013
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/bpb.b110639
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
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.
- リンク情報
- ID情報
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- DOI : 10.1248/bpb.b110639
- ISSN : 0918-6158
- Web of Science ID : WOS:000305868900002