title: Celecoxib interferes to a limited extent with aspirin-mediated inhibition of platelets aggregation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva.
authors.forename: Mark
authors.initials: M
authors.lastname: Ruzov
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva.
authors.forename: Gilad
authors.initials: G
authors.lastname: Rimon
authors.affiliation: Blood Bank & Hematology Institute, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Pikovsky
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva.
authors.forename: David
authors.initials: D
authors.lastname: Stepensky
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001667:Binding, Competitive; D000068579:Celecoxib / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D000068579:Celecoxib; D001241:Aspirin
keywords: COX-1 enzyme; celecoxib; drug−drug interaction; low dose aspirin anti-aggregation effect; pharmacokinetic−pharmacodynamic modelling