Effect of experimental acute renal and hepatic failure on absorption of tacrolimus in rat small intestine
| Autor: | Shinji Yamashita, Shigeki Tamura, Yuji Tokunaga, Atsuo Ohike, Rinta Ibuki, Hitoshi Sezaki, Gordon L. Amidon |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Pharmaceutical Science chemical and pharmacologic phenomena Ileum urologic and male genital diseases digestive system Intestinal absorption Tacrolimus Jejunum Internal medicine Intestine Small medicine Animals Pharmacology (medical) Rats Wistar Pharmacology biology business.industry Metabolism Acute Kidney Injury Liver Failure Acute Rats surgical procedures operative medicine.anatomical_structure Endocrinology Intestinal Absorption Enzyme inhibitor biology.protein Ketoconazole business Perfusion medicine.drug |
| Zdroj: | Drug metabolism and pharmacokinetics. 19(3) |
| ISSN: | 1347-4367 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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