{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:39:36Z","timestamp":1787837976979,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T00:00:00Z","timestamp":1553644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"California Horse Racing Board"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5\u00a0mg\/kg, or saline control. Blood samples were collected up to 72\u00a0hr, analyzed for morphine, and metabolites by LC\/MS\/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine\u20103 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine\u20106 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4\u00a0ng\/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady\u2010state and systemic clearance ranged from 9.40 to 16.9\u00a0L\/kg and 23.3 to 32.4\u00a0ml\u00a0min<jats:sup>\u22121<\/jats:sup>\u00a0kg<jats:sup>\u22121<\/jats:sup>, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites.<\/jats:p>","DOI":"10.1111\/jvp.12759","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T06:46:16Z","timestamp":1553755576000},"page":"401-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses"],"prefix":"10.1111","volume":"42","author":[{"given":"Briana D.","family":"Hamamoto\u2010Hardman","sequence":"first","affiliation":[{"name":"K.L Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine University of California  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene P.","family":"Steffey","sequence":"additional","affiliation":[{"name":"K.L Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine University of California  Davis California"},{"name":"Department of Veterinary Surgery and Radiology School of Veterinary Medicine University of California  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Experimental Therapeutics School of Pharmacy University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"McKemie","sequence":"additional","affiliation":[{"name":"K.L Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine University of California  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Kass","sequence":"additional","affiliation":[{"name":"Department of Medicine and Epidemiology School of Veterinary Medicine University of California  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-4970","authenticated-orcid":false,"given":"Heather K.","family":"Knych","sequence":"additional","affiliation":[{"name":"K.L Maddy Equine Analytical Chemistry Laboratory School of Veterinary Medicine University of California  Davis California"},{"name":"Department of Veterinary Molecular Biosciences School of Veterinary Medicine University of California  Davis California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0739(02)00011-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.67.6.992"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1974161part151"},{"issue":"5","key":"e_1_2_8_5_1","first-page":"870","article-title":"Pharmacokinetics and protein binding of morphine in horses","volume":"44","author":"Combie J. 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