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Cimetidine‐nicoumalone interaction in man: stereochemical considerations.
Author(s) -
Gill TS,
Hopkins KJ,
Bottomley J.,
Gupta SK,
Rowland M.
Publication year - 1989
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.1365-2125.1989.tb05395.x
Subject(s) - cimetidine , pharmacokinetics , pharmacology , enantiomer , oral administration , medicine , regimen , drug interaction , absorption (acoustics) , chemistry , stereochemistry , physics , acoustics
1. The cimetidine‐nicoumalone interaction was studied in five subjects who received a single 10 mg oral dose of racemic nicoumalone alone and 3 days into an oral regimen of cimetidine of 200 mg three times daily and 400 mg at night. 2. The concentrations of R(+)‐ and S(−)− nicoumalone in plasma were measured using a stereospecific h.p.l.c assay; augmentation of prothrombin time was used as a measure of response. 3. Cimetidine increased the rate (but not extent) of absorption of both R(+)‐ and S(−)−nicoumalone, and reduced the clearance of R(+)‐nicoumalone but not that of the S(−)−enantiomer. 4. Cimetidine increased the anticoagulant response produced by nicoumalone in some but not all subjects, despite a consistent effect on the pharmacokinetics of the oral anti‐coagulant. 5. Cimetidine appears to produce its effect by stereoselectively inhibiting the elimination of R(+)‐nicoumalone.