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The aim of this study was to determine the pharmacokinetics of letrozole after a single intravenous administration at three different doses in ewes during the breeding season and its effect on gonadotropins (luteinizing hormone (LH) and follicle\u2010stimulating hormone (FSH)) at the beginning of proestrus. The study was carried out on 24 healthy Merino ewes. Ewes were randomly divided into four groups (<jats:italic>n<\/jats:italic>\u2009=\u20096) as control, 0.5, 1, and 2\u2009mg\/kg. Plasma concentrations of letrozole were measured using HPLC\u2010UV and were analyzed by non\u2010compartmental analysis. LH and FSH concentrations were measured with a commercial ELISA kit. The terminal elimination half\u2013life (<jats:italic>t<\/jats:italic><jats:sub>1\/2\u028ez<\/jats:sub>) was significantly prolonged from 11.82 to 18.44\u2009h in parallel with the dose increase. The dose\u2010normalized area under the concentration\u2013time curve (AUC) increased, and total body clearance (Cl<jats:sub>T<\/jats:sub>) decreased at the 1 and 2\u2009mg\/kg doses (0.05\u2009L\/h\/kg) compared with the 0.5\u2009mg\/kg dose (0.08\u2009L\/h\/kg). There were no differences in the volume of distribution at steady\u2010state and initial (<jats:italic>C<\/jats:italic><jats:sub>0.083h<\/jats:sub>) plasma concentration values between dose groups. The decreased Cl<jats:sub>T<\/jats:sub>, prolonged <jats:italic>t<\/jats:italic><jats:sub>1\/2\u028ez,<\/jats:sub> and increased AUC at increasing doses showed the nonlinear kinetic behavior of letrozole. Letrozole significantly reduced LH concentration without affecting FSH concentration at all doses. As a result, letrozole has the potential to be used in synchronization methods and manipulation of the follicular waves due to its effect on LH secretion.<\/jats:p>","DOI":"10.1111\/jvp.13414","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T07:39:37Z","timestamp":1698997177000},"page":"193-201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-874X","authenticated-orcid":false,"given":"Mehmet Bugra","family":"Kivrak","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gyneacology, Faculty of Veterinary Medicine University of Sivas Cumhuriyet  Sivas Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-2510","authenticated-orcid":false,"given":"Orhan","family":"Corum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6634-0559","authenticated-orcid":false,"given":"Murat","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gyneacology, Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-1774","authenticated-orcid":false,"given":"Erdinc","family":"Turk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1567-991X","authenticated-orcid":false,"given":"Duygu","family":"Durna\u00a0Corum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6845-2279","authenticated-orcid":false,"given":"Ibrahim Ozan","family":"Tekeli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Hatay Mustafa Kemal  Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-4873","authenticated-orcid":false,"given":"Kamil","family":"Uney","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Selcuk  Konya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439\u20100531.2008.01102.x"},{"key":"e_1_2_10_3_1","unstructured":"Anonymous(2023).https:\/\/www.medsafe.govt.nz\/profs\/datasheet\/l\/letroletab.pdf."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani10071208"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2011.02.024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.1150111"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2016.388\u2010395"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smallrumres.2022.106787"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1998.tb04813.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smallrumres.2018.07.019"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.80.7.702"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.13031"},{"key":"e_1_2_10_13_1","first-page":"1","volume-title":"XPharm: The Comprehensive Pharmacology Reference","author":"Dellapasqua S.","year":"2007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.174"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.22456\/1679\u20109216.123760"},{"key":"e_1_2_10_16_1","first-page":"3e9","article-title":"Council Directive 96\/22\/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of \u00df\u2010agonists, and repealing directives 81\/602\/EEC, 88\/146\/EECand88\/299\/EEC","volume":"125","author":"European Commission","year":"1996","journal-title":"Official Journal of the European Communities"},{"key":"e_1_2_10_17_1","unstructured":"European Medicines Agency. 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