Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats.
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.
Trenk
D
D
Division of Clinical Pharmacology, Reha-Zentrum, Bad Krozingen, West Germany.
Winkelmann
B
B
Jähnchen
E
E
Oie
S
S
D015110:4-Hydroxycoumarins / Q000493:pharmacokinetics*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D010644:Phenprocoumon / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D015110:4-Hydroxycoumarins; D002352:Carrier Proteins; D010644:Phenprocoumon