@article{oai:kanazawa-u.repo.nii.ac.jp:00015051,
 author = {石崎, 純子 and 菅, 幸生 and 荒井, 國三 and 崔, 吉道 and 宮本, 謙一 and Ishizaki, Junko and Tsuda, Tomoko and Suga, Yukio and Ito, Satsuki and Arai, Kunizo and Sai, Yoshimichi and Miyamoto, Ken-ichi},
 issue = {7},
 journal = {Biological and Pharmaceutical Bulletin},
 month = {Jul},
 note = {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.},
 pages = {1009--1013},
 title = {Change in pharmacokinetics of mycophenolic acid as a function of age in rats and effect of coadministered amoxicillin/clavulanate},
 volume = {35},
 year = {2012}
}