Interruption of the enterohepatic circulation of indomethacin by cholestyramine in rabbits
| Autor: | A. A. Al-Angary, M. A. Al-Meshal, M.Wafik Gouda, Y. M. El-Sayed, K. M. Lutfi |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Volume of distribution
medicine.medical_specialty Lagomorpha Cholestyramine biology business.industry Central compartment Pharmaceutical Science Pharmacology Drug interaction biology.organism_classification Endocrinology Pharmacokinetics Oral administration Internal medicine medicine business Enterohepatic circulation medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 64:155-160 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/0378-5173(90)90264-5 |
| Popis: | The purpose of this investigation was to determine whether the oral administration of cholestyramine would increase the systemic clearance of indomethacin following intravenous administration (2 mg/kg) to rabbits. In cholestyramine-treated rabbits a significant reduction in indomethacin serum concentration was observed compared to control animals. Cholestyramine treatment resulted in a significant decrease in the terminal elimination half-life (1.26 ± 0.13 and 0.85 ± 0.06 h for the control and treated groups, respectively) and the mean residence time (1.31 ± 0.13 and 0.78 ± 0.04 h for the control and treated rabbits, respectively). Furthermore, a 56% increase in the systemic clearance (1.91 ± 0.17 and 2.99 ± 0.2 ml min −1 kg −1 for the control and treated rabbits, respectively) and 36% decrease in the area under the serum concentration-time curve (17.57 ± 1.62 and 11.19 ± 0.7 μg h ml(su for the control and treated rabbits, respectively) were also observed. Cholestyramine administration did not significantly alter the apparent volume of distribution parameters ( V c , V ss and V area ). Regarding the microconstants of the two-compartment model which adequately described indomethacin kinetic in control and treated rabbits, cholestyramine administration produced a significant increase in the rate of transfer of indomethacin from the tissue compartment (K 21 ) and out of the central compartment ( K 10 ). These findings indicate that cholestyramine administration accelerates the systemic elimination of indomethacin. This effect is thought to be due to augmentation of net biliary excretion through enteric binding. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|