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Cimetidine-nicoumalone interaction in man: stereochemical considerations.
T S Gill1, K J Hopkins, J Bottomley
1Department of Pharmacy, University of Manchester.
British Journal of Clinical Pharmacology
|April 1, 1989
Summary
Cimetidine affects how the body processes nicoumalone, potentially increasing its anticoagulant effect. This interaction appears to be stereoselective, primarily impacting R(+)-nicoumalone elimination.
Area of Science:
- Pharmacology
- Drug Interactions
- Clinical Pharmacy
Background:
- Nicoumalone is an oral anticoagulant.
- Cimetidine is a commonly prescribed medication.
- Potential drug interactions require thorough investigation.
Purpose of the Study:
- To investigate the pharmacokinetic and pharmacodynamic interaction between cimetidine and nicoumalone.
- To determine if cimetidine alters the absorption, clearance, or anticoagulant response to nicoumalone.
Main Methods:
- Five subjects received oral nicoumalone alone and during cimetidine treatment.
- Plasma concentrations of R(+) and S(-) nicoumalone were measured using stereospecific HPLC.
- Prothrombin time was monitored to assess anticoagulant response.
Main Results:
- Cimetidine increased the absorption rate of both nicoumalone enantiomers.
- Cimetidine reduced the clearance of R(+)-nicoumalone but not S(-)-nicoumalone.
- The anticoagulant response to nicoumalone was variably increased by cimetidine.
Conclusions:
- Cimetidine stereoselectively inhibits the elimination of R(+)-nicoumalone.
- This interaction can lead to increased anticoagulant effects in some individuals.
- Clinical monitoring is advised when co-administering cimetidine and nicoumalone.