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Thromb Haemost 1988; 60(01): 035-038
DOI: 10.1055/s-0038-1647630
Original Article
Schattauer GmbH Stuttgart

4-Hydroxycoumarin Oral Anticoagulants : Pharmacokinetics-Response Relationship

H H W Thijssen
1   The Dept. of Pharmacology Medical Faculty, University of Limburg, Maastricht, The Netherlands
,
K Hamulyák
2   The Dept. of Haematology Medical Faculty, University of Limburg, Maastricht, The Netherlands
,
H Willigers
2   The Dept. of Haematology Medical Faculty, University of Limburg, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 26 October 1987

Accepted after revision 28 March 1988

Publication Date:
30 June 2018 (online)

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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 (t½ 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 (t½>24 h) should be preferred.

Key words

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

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