Comparative plasma disposition and anticoagulant activities of racemic phenprocoumon and its metabolites in rats.
The anticoagulant phenprocoumon (PH) and its metabolites 6-hydroxy-, 7-hydroxy- and 4'hydroxy-phenprocoumon (6-OH-PH, 7-OH-PH and 4'-OH-PH, respectively) were separately administered intravenously as racemates to rats in order to measure the potential effects of the major metabolites of PH on coagulation. Plasma samples were assayed for total concentrations of the administered compounds and the corresponding prothrombin times; kinetic parameters and anticoagulant activities were estimated using a pharmacodynamic model based on the rate of synthesis of clotting factors. The relative potencies were in the order PH > 4'-OH-PH > 6-OH-PH > 7-OH-PH the latter showing no activity. Patients on PH therapy showed lower plasma concentrations of metabolites than of PH; in humans the metabolites of PH will not contribute significantly to the overall anticoagulant activity of the drug.
de Vries
J X
JX
Abteilung für Klinische Pharmakologie, Universität, Heidelberg, FRG.
Simon
M
M
Völker
U
U
Walter-Sack
I
I
Weber
E
E
Stegmeier
K
K
D000818:Animals; D001711:Biotransformation; D008297:Male; D015394:Molecular Structure; D010644:Phenprocoumon / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
C080914:7-hydroxyphenprocoumon; C080916:6-hydroxyphenprocoumon; C080917:4'-hydroxyphenprocoumon; D010644:Phenprocoumon