{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:34:21Z","timestamp":1762101261881,"version":"3.38.0"},"reference-count":39,"publisher":"American Veterinary Medical Association (AVMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>Objective<\/jats:bold>\u2014To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses.<\/jats:p>\n<jats:p><jats:bold>Animals<\/jats:bold>\u20146 healthy adult horses.<\/jats:p>\n<jats:p><jats:bold>Procedures<\/jats:bold>\u2014Horses received single doses (each 0.15 mg\/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments\/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography\u2013mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects.<\/jats:p>\n<jats:p><jats:bold>Results<\/jats:bold>\u2014In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL\/min\/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L\/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration.<\/jats:p>\n<jats:p><jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.<\/jats:p>","DOI":"10.2460\/ajvr.73.2.290","type":"journal-article","created":{"date-parts":[[2012,1,26]],"date-time":"2012-01-26T15:42:22Z","timestamp":1327592542000},"page":"290-295","source":"Crossref","is-referenced-by-count":20,"title":["Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses"],"prefix":"10.2460","volume":"73","author":[{"given":"Renata L.","family":"Linardi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley M.","family":"Stokes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Keowen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle L.","family":"Hosgood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Short","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Am J Vet Res","first-page":"1632","article-title":"Cardiopulmonary effects of narcotic agonists and a partial agonist in horses","volume":"39","author":"Muir","year":"1978"},{"key":"ref2","series-title":"Drugs and the performance horse","first-page":"199","article-title":"Horses running happy: fentanyl, morphine, and the other narcotic analgesics. 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