Effect of Experimental Acute Renal and Hepatic Failure on Absorption of Tacrolimus in Rat Small Intestine
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- TAMURA Shigeki
- Fujisawa Pharmaceutical Co., LTD.
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- OHIKE Atsuo
- Fujisawa Pharmaceutical Co., LTD.
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- TOKUNAGA Yuji
- Fujisawa Pharmaceutical Co., LTD.
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- IBUKI Rinta
- Fujisawa Pharmaceutical Co., LTD.
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- AMIDON Gordon. L.
- College of Pharmacy, University of Michigan
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- SEZAKI Hitoshi
- Faculty of Pharmaceutical Sciences, Setsunan University
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- YAMASHITA Shinji
- Faculty of Pharmaceutical Sciences, Setsunan University
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Abstract
The objective of this study is to evaluate the effect of acute renal or hepatic failure on the intestinal absorption of tacrolimus. Simultaneous perfusion study in rat small intestine revealed that the extent of absorption into blood vessels was decreased in the jejunum and the ileum of rat of acute renal failure due to the decrease in the uptake of tacrolimus into enterocytes. In contrast, there observed no significant changes in tacrolimus absorption in rat of acute hepatic failure. Since it has been reported that tacrolimus absorption is regulated mainly by Cytochrome P-450 (CYP) mediated metabolism in the jejunum, but by P-glycoprotein (P-gp) mediated efflux in the ileum, these factors might contribute to the changes in intestinal absorption of tacrolimus in rat of acute renal failure. Enzyme inhibitor, ketoconazole, was co-perfused with tacrolimus to specify the effect of CYP and P-gp. However, since ketoconazole failed to recover the permeability in the jejunum and ileum of rat of acute renal failure, it is considered that the changes in CYP or P-gp functions might not be involved in the decreased uptake of tacrolimus. This type of kinetic study in rats should be valuable to identify the precise mechanisms of drug absorption and the effects of various diseases on it, such as acute renal or hepatic failure.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 19 (3), 190-197, 2004
The Japanese Society for the Study of Xenobiotics
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Details 詳細情報について
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- CRID
- 1390001205181131520
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- NII Article ID
- 130004462933
- 80016771595
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- NII Book ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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- PubMed
- 15499186
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed