The effect of bezafibrate on the fibrinolytic enzyme system and the drug interaction with racemic phenprocoumon.
The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.
D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010644:Phenprocoumon / Q000494:pharmacology* / Q000627:therapeutic use; D010960:Plasminogen Activators
D015110:4-Hydroxycoumarins; D001779:Blood Coagulation Factors; D000960:Hypolipidemic Agents; D010960:Plasminogen Activators; D010644:Phenprocoumon