Τόμος 9 (1991) – Τεύχος 2 – Άρθρο 4 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 9 (1991) – Issue 2 – Article 4 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

9: 101-109 (1991)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

9: 101-109 (1991)

warfarin, mechanism of action, pharmacodynamic drug, pharmacokinetic drug interactions

Warfarin, an oral coumarin anticoagulant, is an indirect antagonist of vitamin K, inhibiting the synthesis of six vitamin K-dependent clotting factors. Clinically warfarin is administered as the racemic mix­ture of two enantiomers, R– and S-warfarin, which differ in both their pharmacodynamics and pharmacokinetics. There is a remarkable intersubject variability concerning the required daily dose of warfarin for the same anti­coagulant activity, which, in connection with the observed interactions with other drugs, and the narrow therapeutic index of warfarin, may increase the anticoagulant effect and the risk of bleeding. The interactions of warfarin with other drugs can be broadly divided into phar­macodynamic and pharmacokinetic. Pharmaco­dynamic interactions affect the absorption of vitamin K, and the synthesis and catabolism of vitamin K-dependent clotting factors, whereas pharmacokinetic interactions affect the absor­ption, protein binding and metabolism of war­farin, which, in turn, affect the unbound concentration of the drug at the receptor site. The most serious interactions with warfarin are those that affect stereoselectively the metabo­lism of the more potent S-enantiomer.

1. Campbell, H.A., Link. K.P.: Stύdies on the haemorrhagic sweet clover disease. The isolation and crystallization of the haemorrhagic agent. J. Biol. Chem. 138: 21 (1941)
2. Stahman, M.A., Heubner, C.F., Link, K.Ρ.: Studies on the haemorrhagic sweet clover disease. Identification and synthesis of the haemorrhagic agent. J. Biol. Chem. 138:.513 (1941)
3. Bingham, J.B., Meyer, O.O., Pohle, F.J.: Studies on the haemorrhagic agent 3,3′-methylene-bis-(4-hydroxycοu­marin). Am. J. Sci., 202: 563 (1941)
4. Link, K.Ρ.: The discovery of dicumarol and its sequels. Circulation 19: 97 (1959)
5. Ikawa, M., Stahmann, M.A., Link, K.P.: Studies on 4-hydrοxycoumarin: Condensation of alpha, beta-un­saturated ketones with 4-hydroxycοumarin. J.A.C.S 66: 902 (1944)