Celecoxib interferes to a limited extent with aspirin‐mediated inhibition of platelets aggregation. (15th December 2015)

• Record Type: Journal Article
• Authors: Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg; Stepensky, David
• Is Part Of: British journal of clinical pharmacology. Volume 81:Number 2(2016:Feb.)
• Page Start: 316
• Page End: 326
• Publication Date: 2015-12-15
• Subjects: celecoxib -- COX‐1 enzyme -- drug−drug interaction -- low dose aspirin anti‐aggregation effect -- pharmacokinetic−pharmacodynamic modelling; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.12801
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : Aims: The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX‐1 binding and its consequences on the aspirin‐mediated antiplatelet effects. Methods: We investigated ex vivo the interaction between celecoxib and aspirin for COX‐1 binding and measured the resulting antiplatelet effects. We applied mechanism‐based pharmacokinetic−pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. Results: The predictions of the PK‐PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day −1 celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. Conclusions: At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX‐1 binding. Interaction between low dose aspirin and other COX‐2 inhibitors and its clinical consequences requires further investigation.