The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies.
The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture. Each subject received a single oral dose of 0.6 mg/kg of racemic, S(-), and R(+) phenprocoumon. S(-) phenprocoumon was 1.6 to 2.6 times as a potent as R(+) phenprocoumon when the area under the effect/time curve was used to quantify the total anticoagulant effect per dose. Comparing the plasma concentrations that elicited the same anticoagulant effect, S(-) phenprocoumon was 1.5 to 2.5 times as potent as R(+) phenprocoumon. The anticoagulant activity of the racemic mixture was between that of the enantiomers. There was no distinct difference in the rate of elimination between the enantiomers. The apparent volume of distribution and the plasma clearance for S(-) phenprocoumon were less than those for R(+) phenprocoumon. When the binding of the enantiomers to human serum albumin was compared, S(-) phenprocoumon was more highly bound than R(+) phenprocoumon. The protein binding of racemic phenprocoumon was between that of the enantiomers. The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution.
D000328:Adult; D000925:Anticoagulants; D003374:Coumarins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D010644:Phenprocoumon / Q000097:blood / Q000494:pharmacology*; D011485:Protein Binding; D011517:Prothrombin Time; D012709:Serum Albumin / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D003374:Coumarins; D012709:Serum Albumin; D010644:Phenprocoumon