4-Hydroxycoumarin Oral Anticoagulants : Pharmacokinetics-Response Relationship

Summary

The blood coagulating factors II and VII and prothrombin times (Thrombotest) were followed during a dosage interval (= 24 h) in patients on acenocoumarol (n = 6) and on phenprocoumon (n = 6) therapy. The patients were on stable anti-coagulation (%TT: 7-13%) for at least 6 months. The study was performed to investigate the concentration-response relationship of the 4-hydroxycoumarin-type oral anticoagulants. The three parameters were stable during the 24-h interval for patients on phenprocoumon therapy. Patients on acenoumarol showed fluctuations in their factor VII levels; peak activities were observed at about 2 h, trough activities at about 16 h after acenocoumarol intake. Factor II and Thrombotest activities were stable. Plasma levels of phenprocoumon were stable during daytime whereas acenocoumarol levels declined exponentially (t_½ about 12 h). The results indicate the oral anticoagulants to exhibit a concentration-response relationship common to drug-receptor interactions. The results also suggest that for stable and long-lasting anticoagulant therapy oral anticoagulants with half-lives beyond the dosage interval (t_½>24 h) should be preferred.

Key words

Oral anticoagulants - Acenocoumarol - Factor VII - Factor II - INR - Thrombotest - Phenprocoumon

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