6533b7d9fe1ef96bd126ceea

RESEARCH PRODUCT

Dose-dependent metabolism and hepatic distribution of phenprocoumon in rats

Dietmar TrenkE. JähnchenSvein ØIeBernhard Winkelmann

subject

Malemedicine.medical_specialtymedicine.drug_classDose dependencePhenprocoumonPharmacokineticsElimination rate constantInternal medicinemedicineAnimalsDistribution (pharmacology)Tissue DistributionPharmacology (medical)General Pharmacology Toxicology and PharmaceuticsVolume of distributionDose-Response Relationship DrugChemistryAnticoagulantRats Inbred Strains4-HydroxycoumarinsMetabolismRatsEndocrinologyLiverInjections IntravenousPhenprocoumonCarrier Proteinsmedicine.drug

description

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.

yearjournalcountryeditionlanguage
1988-02-01Journal of Pharmacokinetics and Biopharmaceutics
https://doi.org/10.1007/bf01061859