Journal article
Investigation into the causes of aspirin resistance in healthy dogs
Journal of veterinary pharmacology and therapeutics, Vol.42(2), pp.160-170
03/2019
Handle:
https://hdl.handle.net/2376/109635
PMID: 30302763
Abstract
Antiplatelet effects of acetylsalicylic acid (ASA, aspirin) may be poor in some individuals. Additionally, no method exists for predicting poor ASA response (resistance) in individual dogs. This study's main objective was to determine whether poor ASA response results from pharmacodynamic or pharmacokinetic causes. ASA concentrations causing 50% inhibition of platelet aggregation (in vitro IC50) were determined using whole blood collected from 21 drug‐free healthy dogs to evaluate intrinsic sensitivity of platelets to ASA. Dogs were then administered ASA at 4 mg/kg once orally. Percent decrease in platelet aggregation from baseline, and plasma ASA and salicylic acid (SA) concentrations (expressed as AUC values) were measured for up to 3 hr. By 3 hr, 13/21 (62%) dogs showed >50% aggregation inhibition, while 8/21 (38%) dogs showed <50% inhibition. Aggregation inhibition values were negatively correlated with in vitro IC50 values (Rs = −0.49; p = 0.028) and positively correlated with ASA concentrations (Rs = 0.48; p = 0.03). Furthermore, ASA concentrations were strongly negatively correlated (Rs = −0.88; p < 0.001) with SA/ASA concentration ratios, an index of ASA metabolism to SA by esterase enzymes. Multiple linear regression analysis indicated that 59% (p < 0.001) of interindividual variability in aggregation inhibition was explained by in vitro IC50 values (29% of variability) and ASA concentrations (29% of variability). Consequently, poor in vivo ASA response in these dogs resulted from both pharmacodynamic (decreased platelet sensitivity) and pharmacokinetic (lower ASA concentrations) causes. Lower ASA concentrations may be explained by reduced bioavailability associated with higher esterase activities.
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Details
- Title
- Investigation into the causes of aspirin resistance in healthy dogs
- Creators
- Jillian M Haines - Washington State UniversityPamela M Lee - Washington State UniversityRachel M Hegedus - Washington State UniversityJulianne K Hwang - Washington State UniversityMichael H Court - Washington State University
- Publication Details
- Journal of veterinary pharmacology and therapeutics, Vol.42(2), pp.160-170
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Number of pages
- 11
- Grant note
- Washington State University College of Veterinary Medicine Intramural Grant
- Identifiers
- 99900547478801842
- Language
- English
- Resource Type
- Journal article