| Autor: |
Giacomini, Kathleen M., Nakeeb, Shaheen M., Levy, Gerhard |
| Zdroj: |
Journal of Pharmaceutical Sciences; July 1980, Vol. 69 Issue: 7 p786-789, 4p |
| Abstrakt: |
The elimination kinetics and systemic availability of d-propoxyphene were determined in dogs before and after construction of a portacaval shunt. For this purpose, the drug was administered intravenously and orally, in aqueous solution, according to a balanced experimental design. The total plasma clearance of propoxyphene ranged from 14.4 to 31.8 ml/min/kg before the shunt and decreased appreciably in two of four dogs after shunting. There was no significant change in the serum protein binding of the drug. The systemic availability increased from an average of 25% before to an average of 54% after shunting (p< 0.05). The ratio of areas under the plasma concentration–time curve of norpropoxyphene to propoxyphene was not significantly affected by the shunt when propoxyphene was administered intravenously; it decreased substantially after shunting when the drug was administered orally. Pharmacokinetic analysis indicates that orally administered propoxyphene is subject to prehepatic as well as hepatic first-pass elimination in dogs. The magnitude of the first-pass effect is similar to that in humans. These results suggest that the dosage of orally administered propoxyphene should be reduced in patients with portacaval shunt or with cirrhosis of the liver. |
| Databáze: |
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