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Stereoselective interaction between the R enantiomer of warfarin and cimetidine.
Author(s) -
Choonara IA,
Cholerton S.,
Haynes BP,
Breckenridge AM,
Park BK
Publication year - 1986
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1986.tb05190.x
Subject(s) - cimetidine , warfarin , stereoselectivity , enantiomer , pharmacokinetics , pharmacology , chemistry , drug interaction , vitamin , medicine , stereochemistry , biochemistry , atrial fibrillation , catalysis
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.