title: No Effect of Omega-3 Carboxylic Acids on Pharmacokinetics/Pharmacodynamics of Warfarin or on Platelet Function When Co-administered with Acetylsalicylic Acid: Results of Two Phase I Studies in Healthy Volunteers.
abstract: BACKGROUND
  Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels.
  
  
  OBJECTIVE
  Our objective was to assess the effects of OM3-CA on warfarin pharmacokinetics and pharmacodynamics and on acetylsalicylic acid (ASA)-dependent and independent platelet activation when co-administered with ASA in two phase I studies.
  
  
  METHODS
  In ECLIPSE II (NCT01431690), 26 participants received warfarin 25 mg on days 1 and 22 and OM3-CA 4 g once daily from day 8 to day 28. In OM-EPA-007 (NCT01486433), 52 participants received simvastatin 40 mg plus ASA 81 mg once daily for 14 days, with or without OM3-CA 4 g. Lack of a drug-drug interaction was indicated when 90% confidence intervals (CIs) fell entirely within the range 80-125% for least-squares mean (LSM) ratios of area under the concentration-time curve (AUC), maximum observed plasma concentration (Cmax), international normalized ratio (INR) AUC to 168 h and maximum INR.
  
  
  RESULTS
  In ECLIPSE II, 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for AUC and Cmaxof S- and R-warfarin enantiomers. The 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for INR AUC to 168 h after dosing and for maximum INR of warfarin. In OM-EPA-007, no significant effect of OM3-CA was observed on ASA-dependent or ASA-independent platelet activation. No deaths or serious adverse events occurred in either study.
  
  
  CONCLUSIONS
  OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA. OM3-CA did not affect platelet function when co-administered with ASA.
authors.affiliation: Certara Strategic Consulting, 2000 Peel Street, Suite 570, Montreal, QC, H3A 2W5, Canada. elliot.offman@certara.com.
authors.forename: Elliot
authors.initials: E
authors.lastname: Offman
authors.affiliation: University of Chicago Pritzker School of Medicine, Chicago, IL, USA.|Corvidia Therapeutics, Waltham, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
authors.affiliation: AstraZeneca Gothenburg, Mölndal, Sweden.
authors.forename: Catarina
authors.initials: C
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects*; D002264:Carboxylic Acids / Q000008:administration & dosage*; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests / Q000379:methods; D019821:Simvastatin / Q000008:administration & dosage; D014859:Warfarin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D002264:Carboxylic Acids; D014859:Warfarin; D019821:Simvastatin; D001241:Aspirin