The possible clinical impact of risperidone on P-glycoprotein-mediated transport of tacrolimus: A case report and in vitro study

Nao Watanabe, Hiroki Higashi, Saki Nakamura, Keiko Nomura, Yuichi Adachi, Masato Taguchi*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

7 被引用数 (Scopus)

抄録

The authors encountered the case of an 8-fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). It was hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by voriconazole and P-glycoprotein (P-gp) inhibition of the small intestine by risperidone exerted a synergistic effect on the bioavailability of tacrolimus. The aim of the present study was to evaluate the effect of risperidone on the P-gp-mediated transport of tacrolimus. The transcellular transport of P-gp substrates was examined in Caco-2 and P-gp-expressing renal epithelial LLC-GA5-COL150 cells. In Caco-2 cells, the apical-basal (A-B) transport of rhodamine123 (Rh123) after a 120 min incubation was increased by 47.1%, whereas that in the B-A direction was decreased by 61.7% in the presence of risperidone (100 μm). These results indicate that risperidone showed an inhibitory effect on the P-gp-mediated transport of Rh123. In LLC-GA5-COL150 cells, the A-B transport of tacrolimus after 120 min incubation was increased by 21.7% in the presence of risperidone (100 μm), whereas that in the B-A direction was decreased by 10.7%. These results suggest that risperidone was at least partly involved in the mechanism of the marked increase in the C/D ratio of tacrolimus. This case report provides new insights into the diversity of drug interactions of tacrolimus triggered by the combination of two concomitant drugs.

本文言語英語
ページ(範囲)30-37
ページ数8
ジャーナルBiopharmaceutics and Drug Disposition
39
1
DOI
出版ステータス出版済み - 2018/01

ASJC Scopus 主題領域

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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