6533b7d3fe1ef96bd1261419

RESEARCH PRODUCT

Factors responsible for interindividual differences in the dose requirement of phenprocoumon

Svein ØIeT. MeinertzEberhard JähnchenH. AlthenDietmar Trenk

subject

Malemedicine.medical_specialtymedicine.drug_classIndividualityPhenprocoumonPharmacokineticsInternal medicinemedicineHumansPharmacology (medical)Myocardial infarctionDosingPharmacologyChemistryCoronary ThrombosisAnticoagulant4-HydroxycoumarinsGeneral MedicineMiddle Agedmedicine.diseaseThrombosisCardiac surgeryEndocrinologyPhenprocoumonProthrombin TimeCardiologyFemaleProtein Bindingmedicine.drugSurgical patients

description

The total and unbound plasma concentrations of phenprocoumon and the prothrombin complex activity were determined in 51 patients on phenprocoumon. A 7-fold difference in the dosing rate (10-70 micrograms/kg/day) was required to maintain the prothrombin complex activity at 11-30% of normal. The variation in dosing requirement was mainly due to interindividual differences in the intrinsic clearance of phenprocoumon and only to a minor degree to differences in sensitivity to it. On average patients with myocardial infarction required only 2/3 of the daily dose of phenprocoumon of post cardiac surgery patients and patients with thrombosis and emboli. That difference appeared to be due to higher clearance in surgical patients and to greater resistance to phenprocoumon in patients with thrombosis and emboli. The total clearance in patients varied approximately 5-fold. It was better predicted by the interindividual intrinsic clearance (r = 0.84) than by the unbound fraction (r = 0.15).

https://doi.org/10.1007/bf00610379