Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia

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dc.contributor.authorMercer, Melissa A.en
dc.contributor.authorDavis, Jennifer L.en
dc.contributor.authorMcKenzie, Harold C.en
dc.contributor.authorMessenger, Kristen M.en
dc.contributor.authorSchaefer, Emilyen
dc.contributor.authorCouncil-Troche, R. McAlisteren
dc.contributor.authorWerre, Stephen R.en
dc.date.accessioned2023-08-23T13:21:20Zen
dc.date.available2023-08-23T13:21:20Zen
dc.date.issued2023-03-01en
dc.date.updated2023-08-22T18:19:02Zen
dc.description.abstractBackground: Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objectives: To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Animals: Eight university owned research horses with experimentally induced endotoxemia. Methods: Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay. Results: Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6 ± 0.3 hour after administration. At 4 and 6 hours after treatment, both APAP (P = <.001, P =.03, respectively) and FLU (P =.0045 and P <.001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6 hours (P =.004 and P =.04), and PLAC at 4 hours (P =.05) after treatment. Conclusions and Clinical Importance: The pharmacokinetics of acetaminophen in endotoxemic horses differ from those reported by previous studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.en
dc.description.versionPublished versionen
dc.format.extentPages 718-727en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1111/jvim.16663en
dc.identifier.eissn1939-1676en
dc.identifier.issn0891-6640en
dc.identifier.issue2en
dc.identifier.orcidMercer, Melissa [0000-0002-8112-5547]en
dc.identifier.orcidMcKenzie, Harold [0000-0001-8230-2237]en
dc.identifier.orcidDavis, Jennifer [0000-0002-7930-4589]en
dc.identifier.orcidCouncil-Troche, Roberto [0000-0002-5741-1535]en
dc.identifier.pmid36840424en
dc.identifier.urihttp://hdl.handle.net/10919/116090en
dc.identifier.volume37en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/36840424en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectacetaminophenen
dc.subjectfeveren
dc.subjecthorseen
dc.subjectpyrexiaen
dc.subject3009 Veterinary Sciencesen
dc.subject30 Agricultural, Veterinary and Food Sciencesen
dc.subjectInfectious Diseasesen
dc.subjectHematologyen
dc.subjectClinical Researchen
dc.subjectClinical Trials and Supportive Activitiesen
dc.subjectEmerging Infectious Diseasesen
dc.subjectBrain Disordersen
dc.subjectSepsisen
dc.subjectDigestive Diseasesen
dc.subject6.1 Pharmaceuticalsen
dc.subject6 Evaluation of treatments and therapeutic interventionsen
dc.subject.meshAnimalsen
dc.subject.meshHorsesen
dc.subject.meshEndotoxemiaen
dc.subject.meshHorse Diseasesen
dc.subject.meshAcetaminophenen
dc.subject.meshChromatography, Liquiden
dc.subject.meshCross-Over Studiesen
dc.subject.meshTandem Mass Spectrometryen
dc.titlePharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemiaen
dc.title.serialJournal of Veterinary Internal Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2023-02-03en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Large Animal Clinical Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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