Mechanism of ticrynafen potentiation of coumarin anticoagulant action.

Abstract

Administration of the antihypertensive drug ticrynafen [2,3-dichloro-4-(2-thienylcarbonyl)-phenoxyacetic acid] has been reported to potentiate the effects of coumarin anticoagulants and to have caused hemorrhagic incidents in some patients. This drug interaction has now been reproduced in the rat. Ticrynafen administration enhanced the degree of hypoprothrombinemia and altered plasma and hepatic vitamin K epoxide concentrations in warfarin-treated rats. Ticrynafen did not affect vitamin K-dependent carboxylase or vitamin K epoxide reductase activities in vitro. Cytosolic DT-diaphorase was very sensitive to ticrynafen inhibition in vitro, and inhibition of vitamin K reduction via this enzyme is a possible mechanism by which ticrynafen potentiates coumarin anticoagulant action. Inhibition of this enzyme may also contribute to the reported hepatotoxicity of ticrynafen.

• Authors: P C Preusch, J W Suttie
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 32 Issue 16 Pg. 2393-8 (Aug 15 1983) ISSN: 0006-2952 [Print] England
• PMID: 6615542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Coumarins
• Glycolates
• Vitamin K
• Quinone Reductases
• Ticrynafen

Topics

• Animals
• Blood Coagulation (drug effects)
• Coumarins (pharmacology)
• Drug Synergism
• Glycolates (toxicity)
• Male
• Quinone Reductases (antagonists & inhibitors)
• Rats
• Rats, Inbred Strains
• Ticrynafen (toxicity)
• Vitamin K (metabolism)