4-Hydroxycoumarin oral anticoagulants: pharmacokinetics-response relationship.
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 anticoagulation (%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 (t1/2 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 (t1/2 greater than 24 h) should be preferred.
Thijssen
H H
HH
Dept. of Pharmacology, Medical Faculty, University of Limburg, Maastricht, The Netherlands.
Hamulyák
K
K
Willigers
H
H
D015110:4-Hydroxycoumarins / Q000493:pharmacokinetics*; D000074:Acenocoumarol / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005167:Factor VII / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D010644:Phenprocoumon / Q000493:pharmacokinetics*; D011516:Prothrombin / Q000032:analysis
D015110:4-Hydroxycoumarins; D005167:Factor VII; D011516:Prothrombin; D000074:Acenocoumarol; D010644:Phenprocoumon