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. 1989 Apr;27(4):469–474. doi: 10.1111/j.1365-2125.1989.tb05395.x

Cimetidine-nicoumalone interaction in man: stereochemical considerations.

T S Gill 1, K J Hopkins 1, J Bottomley 1, S K Gupta 1, M Rowland 1
PMCID: PMC1379726  PMID: 2719902

Abstract

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.

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Selected References

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