Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats |
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Authors: | D Trenk B Winkelmann E J?hnchen S Oie |
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Institution: | Division of Clinical Pharmacology, Reha-Zentrum, Bad Krozingen, West Germany. |
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Abstract: | The dose-dependency of phenprocoumon disposition was determined in rats by iv administration of 0.1 and 1.0 mg/kg doses to separate groups of animals. The intrinsic clearance (unbound clearance) was 33% lower in the animals given 1.0 mg/kg dose than in the animals given 0.1 mg/kg dose. The apparent unbound volume of distribution was 55% lower and the elimination rate constant 54% higher in the high dose group than in the lower dose group. Binding of phenprocoumon to liver showed saturability with a two- to threefold higher apparent unbound fraction of phenprocoumon in liver in animals given the high dose in comparison to animals given the low dose. |
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