title: Competition between low-dose aspirin and other NSAIDs for COX-1 binding and its clinical consequences for the drugs' antiplatelet effects.
abstract: BACKGROUND
  NSAIDs are frequently used in modern medicine to inhibit the COX enzymes and induce analgesic, antipyretic, anti-inflammatory, and antiplatelet effects. Concomitant treatment with two or more NSAIDs can lead to their competition for binding and inhibition of the COX enzymes and altered time course of the pharmacological effects.
  
  
  METHODS
  The competition between the low-dose aspirin and other NSAIDs for binding to COX-1 is described, including the recent findings on the differences in the interaction of NSAIDs with the individual COX-1 subunits, and the clinical consequences of this drug-drug interaction. The major pharmacokinetic (PK) and pharmacodynamic (PD) factors that govern the interaction of low-dose aspirin with other NSAIDs are explained, along with the approaches for prediction of the magnitude of this interaction using mechanism-based PK-PD modeling.
  
  
  CONCLUSIONS
  Concomitant administration of other NSAIDs can diminish the antiplatelet effects of low-dose aspirin, increase the risk of thromboembolic effects (heart attacks and strokes), and lead to patient morbidity and mortality. The healthcare providers and the patients are seldom aware to this clinical problem and its consequences. Despite this drug interaction, low-dose aspirin possesses high clinical safety and it is not expected to be replaced by the recently approved drugs.
authors.affiliation: Ben-Gurion University of the Negev, Department of Clinical Biochemistry and Pharmacology, The Faculty of Health Sciences , P.O.Box 653, Beer Sheva 84105 , Israel +972 8 6477381 ; davidst@bgu.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Stepensky
authors.forename: Gilad
authors.initials: G
authors.lastname: Rimon
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology*; D003461:Crystallography; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017433:Protein Structure, Secondary
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D001241:Aspirin
keywords: COX-1 and COX-2 enzymes; NSAIDs; dose- and treatment schedule-dependent effects; drug–drug interaction; pharmacokinetic-pharmacodynamic modeling