{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:33:37Z","timestamp":1754145217815,"version":"3.41.2"},"reference-count":40,"publisher":"American Veterinary Medical Association (AVMA)","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine the pharmacokinetics of acetaminophen (<jats:italic>N<\/jats:italic>-acetyl-para-aminophenol [APAP]) and its metabolites after oral administration of a single dose of APAP, with or without silymarin or <jats:italic>N<\/jats:italic>-acetylcysteine (NAC), to orange-winged Amazon parrots (<jats:italic>Amazona amazonica<\/jats:italic>).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Eight parrots received, in 3 separate studies, 1 of the following oral treatments: (1) APAP (100 mg\/kg) with silymarin (50 mg\/kg, twice, q 12 h); (2) APAP (100 mg\/kg) with NAC (400 mg\/kg); or (3) APAP (100 mg\/kg) alone. For each study, blood samples were collected over 24 hours after drug administration to evaluate plasma concentrations of APAP, APAP-glucuronide, and APAP-sulfate. Pharmacokinetic parameters were calculated. Plasma biochemistry panels were performed before and after each study. In a fourth study, a single oral dose of APAP (100 mg\/kg) was administered to 8 additional parrots for adverse effects evaluation alone.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>Pharmacokinetic parameters for APAP, APAP-glucuronide, and APAP-sulfate were established. The APAP maximum plasma concentration, time of maximal plasma concentration, and half-life across studies ranged from 2,016.9 to 2,917.2 ng\/mL, 1.13 to 2.1 hours, and 1.3 to 1.45 hours, respectively. Acetaminophen had marked metabolism to APAP-glucuronide and negligible to APAP-sulfate. Concurrent administration of APAP with silymarin resulted in a mild but significant elevation in glutamate dehydrogenase.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Acetaminophen plasma concentrations were lower than in other avian species despite a relatively high dose. Acetaminophen has fast absorption, short half-life, and marked glucuronidation. Single oral dose administration of APAP, alone or with NAC, appears safe based on plasma biochemistries. Multidose and pharmacodynamic studies are needed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>This is the first pharmacokinetic study of APAP in psittacines, which has the potential to be an effective and safe component of multimodal analgesia in these species.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.12.0402","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T14:42:55Z","timestamp":1742827375000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of single-dose oral acetaminophen with and without concurrent administration of silymarin or N-acetylcysteine in orange-winged Amazon parrots (Amazona amazonica)"],"prefix":"10.2460","volume":"86","author":[{"given":"Lucyanne","family":"Megan","sequence":"first","affiliation":[{"name":"William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Sanchez-Migallon Guzman","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Knych","sequence":"additional","affiliation":[{"name":"K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3612-5548","authenticated-orcid":true,"given":"Hugues","family":"Beaufr\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"4","key":"B1","series-title":"Temp Austin Tex","first-page":"351","article-title":"Paracetamol (acetaminophen): a familiar drug with an unexplained mechanism of action","volume":"8","author":"Ayoub SS","year":"2021","unstructured":"Ayoub SS. Paracetamol (acetaminophen): a familiar drug with an unexplained mechanism of action. Temp Austin Tex. 2021;8(4):351\u2013371."},{"issue":"8","key":"B2","series-title":"Pharmacogenet Genomics","first-page":"416","article-title":"PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses","volume":"25","author":"Mazaleuskaya LL","year":"2015","unstructured":"Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015;25(8):416\u2013426."},{"key":"B3","series-title":"Front Pharmacol","first-page":"580289","article-title":"Analgesic effect of acetaminophen: a review of known and novel mechanisms of action","volume":"11","author":"Ohashi N","year":"2020","unstructured":"Ohashi N, Kohno T. Analgesic effect of acetaminophen: a review of known and novel mechanisms of action. 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