The colon displays an absorptive capacity of tacrolimus

K. Nishi, T. Ishii, M. Wada, S. Amae, N. Sano, M. Nio, Y. Hayashi

研究成果: Article

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Purpose In our previous study, blood levels of orally administered tacrolimus were significantly higher in short bowel piglets than in control animals. It has been reported that the blood levels of tacrolimus are influenced by the metabolic activity of intestinal CYP3A4. If tacrolimus may be absorbed in the colon, direct administration of drug into this organ might be useful to augment bioavailability since the expression of CYP3A4 is low at this site. In the present study we evaluated the absorptive capacity of tacrolimus in the colon. Materials and methods Piglets were divided into four groups: groups 1 and 2 were controls (n = 11 and 3, respectively); group 3 underwent resection of the entire small intestine (n = 8); and group 4 had a catheter placed in the cecum (n = 4). In groups 1 and 3, tacrolimus was administered orally; in group 2 it was given intravenously; and in group 4 it was injected into cecum through the catheter from postoperative days 3 to 7. On day 7, blood samples were obtained for drug measurements to calculate the area under the concentration time curve (AUC) values. Results The trough level and AUC values of tacrolimus in group 4 as well as in group 3 were significantly higher than those in group 1. In Group 4 animals showed a 60-minute time to peak concentration. Conclusions Tacrolimus is absorbed by the colon. Since the blood levels were not influenced by the metabolic activity in the graft bowel, direct administration of tacrolimus into the colon might be useful in small intestinal transplantation.

元の言語English
ページ(範囲)364-366
ページ数3
ジャーナルTransplantation Proceedings
36
発行部数2
DOI
出版物ステータスPublished - 2004 3

ASJC Scopus subject areas

  • Surgery
  • Transplantation

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