{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:06:32Z","timestamp":1790762792749,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011910","name":"Deutsche Reiterliche Vereinigung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011910","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre\u2010medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti\u2010doping rule violation. Therefore, a pharmacokinetic study on 6\u00a0horses was conducted using a single intravenous (IV) dose of 0.2\u00a0mg\/kg DIA Plasma and urine samples were collected at specified intervals until 16 and 26\u00a0days post\u2010administration, respectively. Samples were analysed by a sensitive liquid chromatography\u2013electrospray ionization\/tandem mass spectrometry method. DIA showed a triphasic elimination pattern in the horse. The mean plasma clearance of DIA was 5.9\u00a0ml\/min\/kg, and the plasma elimination half\u2010life in the terminal phase was 19.9\u00a0h. Applying the Toutain model approach, an effective plasma concentration of DIA was estimated at 24\u00a0ng\/ml, and irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were computed to 0.047 and 0.1\u00a0ng\/ml, respectively. The detection time according to the European Horserace Scientific Liaison Committee (EHSLC), that is the time for which observed DIA plasma concentrations of all investigated horses were below the IPC was 10\u00a0days. Using Monte Carlo Simulations, it was estimated that concentrations of DIA in plasma would fall below the IPC 18\u00a0days after the DIA administration for 90% of horses. However, in the present study, a single administration of DIA could be detected for 24\u00a0days in urine via the presence of OXA, its dominant metabolite.<\/jats:p>","DOI":"10.1111\/jvp.12991","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T08:28:32Z","timestamp":1623400112000},"page":"733-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-3466","authenticated-orcid":false,"given":"Ina","family":"Schenk","sequence":"first","affiliation":[{"name":"Institute of Biochemistry Center for Preventive Doping Research German Sport University Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Machnik","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Center for Preventive Doping Research German Sport University Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Broussou","sequence":"additional","affiliation":[{"name":"INTHERES, INRAE, ENVT Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Meuly","sequence":"additional","affiliation":[{"name":"INTHERES, INRAE, ENVT Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice B.","family":"Roques","sequence":"additional","affiliation":[{"name":"INTHERES, INRAE, ENVT Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-4611","authenticated-orcid":false,"given":"Elodie","family":"Lallemand","sequence":"additional","affiliation":[{"name":"INTHERES, INRAE, ENVT Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"D\u00fce","sequence":"additional","affiliation":[{"name":"Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helma","family":"R\u00f6ttgen","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Center for Preventive Doping Research German Sport University Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Lagershausen","sequence":"additional","affiliation":[{"name":"German Equestrian Federation Warendorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8846-8892","authenticated-orcid":false,"given":"Pierre\u2010Louis","family":"Toutain","sequence":"additional","affiliation":[{"name":"INTHERES, INRAE, ENVT Universit\u00e9 de Toulouse Toulouse France"},{"name":"Comparative Biomedical Sciences The Royal Veterinary College University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-6451","authenticated-orcid":false,"given":"Mario","family":"Thevis","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Center for Preventive Doping Research German Sport University Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14069"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20107158.1987.tb03404.x"},{"key":"e_1_2_10_4_1","volume-title":"Dosierungsvorschl\u00e4ge f\u00fcr Arzneimittel bei Pferden: Mit zahlreichen tabellarischen \u00dcbersichten (3., vollst.aktualisierte und erw. Aufl)","author":"Halbmayr E.","year":"2009"},{"key":"e_1_2_10_5_1","unstructured":"International Federation of Horseracing Authorities(2020).IFHA.https:\/\/www.ifhaonline.org\/default.asp?section=IABRW&area=4"},{"issue":"3","key":"e_1_2_10_6_1","first-page":"171","article-title":"Diazepam and doping in horse","volume":"141","author":"Jaussaud P.","year":"1990","journal-title":"Revue De M\u00e9decine V\u00e9t\u00e9rinaire"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200746040\u201000001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4557-4555-5.00087-X"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010007\u20101297\u20109"},{"key":"e_1_2_10_10_1","first-page":"117","volume-title":"Pharmakotherapie bei Haus\u2010 und Nutztieren","author":"L\u00f6scher W.","year":"2014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/23.1.29"},{"issue":"10","key":"e_1_2_10_12_1","first-page":"1756","article-title":"Pharmacodynamic and pharmacokinetic properties of diazepam in horses","volume":"43","author":"Muir W. 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