Article date: April 1989
By: TS Gill, KJ Hopkins, J. Bottomley, SK Gupta, M. Rowland, in Volume 27, Issue 4, pages 469-474
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.
DOI: 10.1111/j.1365-2125.1989.tb05395.x
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