title: Pharmacokinetic and pharmacodynamic interactions of aspirin with warfarin in beagle dogs.
abstract: 1. Warfarin and aspirin are widely used in a wide spectrum of thromboembolic and atherothrombotic diseases. Despite the potential efficacy of warfarin-aspirin therapy, the safety and side effect of combined therapy remains unclear. 2. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic interactions between warfarin and aspirin in beagles after single and multiple doses. 3. Coadministration of aspirin had no significant effects on the area under the plasma concentration time curve (AUC(0-t)) and maximum plasma concentration (Cmax) of R- and S-warfarin after a single dose of warfarin, but significantly increase the AUC(0-t) and Cmax and dramatically decrease the clearance (CL) of R- and S-warfarin after multiple dose of warfarin. Accordingly, there was a slight increase in the AUEC(0-t) and Emax of activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) after multiple dose of warfarin. 4. Coadministration of warfarin had no markedly effects on the AUC(0-t) and Cmax of aspirin and its metabolite salicylic acid after single or multiple dose of aspirin. Meanwhile, the AUEC(0-t) and Emax of inhibition of platelet aggregation (IPA) were not significantly affected by warfarin. 5. Our animal study indicated that coadministration of aspirin with warfarin can cause significant pharmacokinetic and pharmacodynamic drug-drug interactions in beagles. However, more studies are urgently needed to assess related information of warfarin-aspirin drug interactions in healthy volunteers or patients.
authors.affiliation: a Department of Basic and Clinical Pharmacology , School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .|b Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Chenlin
authors.initials: C
authors.lastname: Shen
authors.affiliation: a Department of Basic and Clinical Pharmacology , School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.affiliation: b Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: a Department of Basic and Clinical Pharmacology , School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a Department of Basic and Clinical Pharmacology , School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: a Department of Basic and Clinical Pharmacology , School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: b Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.affiliation: c Department of Parasitology , Provincial Laboratory of Microbiology & Parasitology and the Key Laboratory of Zoonoses Anhui, Anhui Medical University , Hefei , Anhui , China .
authors.forename: Faustina
authors.initials: F
authors.lastname: Pappoe
authors.affiliation: d Center for Drug Clinical Research, Shanghai University of Chinese Medicine , Shanghai , China , and.
authors.forename: Jihan
authors.initials: J
authors.lastname: Huang
authors.affiliation: e Department of Cardiology , the First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Tang
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019934:International Normalized Ratio; D008297:Male; D010314:Partial Thromboplastin Time; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011517:Prothrombin Time; D012015:Reference Standards; D020156:Salicylic Acid / Q000097:blood; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D020156:Salicylic Acid; D001241:Aspirin
keywords: Aspirin; R- and S-warfarin; drug–drug interaction; pharmacodynamics; pharmacokinetic; salicylic acid