Biliary excretion of warfarin metabolites and their metabolism by rat gut flora. |
| |
Authors: | M L Powell B Pope G W Elmer W F Trager |
| |
Institution: | Department of Pharmaceutical Sciences, School of Pharmacy University of Washington Seattle, Washington 98195, USA |
| |
Abstract: | The bile was determined to be the major excretory route for 14C-warfarin in the rat with approximately 10% of the administered dose excreted within 5 hours after injection. Relatively little radioactivity appeared in the faces, indicating that considerable enterohepatic recycling was taking place. Less than 4% of the radioactivity in the bile could be extracted with organic solvents. Following incubation of the bile with β-glucuronidase or rat gut flora, however, the bulk of the radioactivity was extractable. The extent of gut flora-mediated hydrolysis of these polar biliary warfarin conjugates was approximately the same as obtained with β-glucuronidase. Approximately of the gut flora-hydrolyzable conjugates were labile and subject to nonenzymatic hydrolysis at 37 C for 24 h. Chromatographic examination of the extracts from β-glucuronidase-treated bile revealed the presence of warfarin and 4′-, 6-, 7-, and 8-hydroxywarfarin. Warfarin and 7-hydroxywarfarin were the most abundant metabolites in the extracts. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|