vitamin-k-1 and Bradycardia

The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma half-life of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-1) (P less than 0.02). Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case.

Topics: Administration, Oral; Bradycardia; Cimetidine; Drug Eruptions; Drug Interactions; Half-Life; Humans; Hypotension; Injections, Intravenous; Kinetics; Protein Binding; Prothrombin Time; Random Allocation; Stereoisomerism; Vitamin K 1; Warfarin