Pharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season

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dc.authoridTURK, ERDINC/0000-0003-1735-1774
dc.authoridUney, Kamil/0000-0002-8674-4873
dc.authoridKIVRAK, MEHMET BUGRA/0000-0002-4772-874X
dc.authoridCorum, Orhan/0000-0003-3168-2510
dc.contributor.authorKivrak, Mehmet Bugra
dc.contributor.authorCorum, Orhan
dc.contributor.authorYuksel, Murat
dc.contributor.authorTurk, Erdinc
dc.contributor.authorCorum, Duygu Durna
dc.contributor.authorTekeli, Ibrahim Ozan
dc.contributor.authorUney, Kamil
dc.date.accessioned2024-10-26T18:07:41Z
dc.date.available2024-10-26T18:07:41Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractLetrozole is a non-steroidal, third-generation aromatase inhibitor used in humans. Although letrozole is not approved for use in animals, it is used off-label in cases of synchronization and infertility. 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-stimulating hormone (FSH)) at the beginning of proestrus. The study was carried out on 24 healthy Merino ewes. Ewes were randomly divided into four groups (n = 6) as control, 0.5, 1, and 2 mg/kg. Plasma concentrations of letrozole were measured using HPLC-UV and were analyzed by non-compartmental analysis. LH and FSH concentrations were measured with a commercial ELISA kit. The terminal elimination half-life (t(1/2 lambda z)) was significantly prolonged from 11.82 to 18.44 h in parallel with the dose increase. The dose-normalized area under the concentration-time curve (AUC) increased, and total body clearance (Cl-T) decreased at the 1 and 2 mg/kg doses (0.05 L/h/kg) compared with the 0.5 mg/kg dose (0.08 L/h/kg). There were no differences in the volume of distribution at steady-state and initial (C-0.083h) plasma concentration values between dose groups. The decreased ClT, prolonged t(1/2 lambda z), 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.
dc.description.sponsorshipThis study was supported by the Coordination of Scientific Research Projects, University of Hatay Mustafa Kemal, Turkiye (Project No. 20.M.031). [20]; Coordination of Scientific Research Projects, University of Hatay Mustafa Kemal
dc.description.sponsorshipThis study was supported by the Coordination of Scientific Research Projects, University of Hatay Mustafa Kemal, Turkiye (Project No. 20.M.031).
dc.identifier.doi10.1111/jvp.13414
dc.identifier.endpage201
dc.identifier.issn0140-7783
dc.identifier.issn1365-2885
dc.identifier.issue3
dc.identifier.pmid37920137
dc.identifier.startpage193
dc.identifier.urihttps://doi.org/10.1111/jvp.13414
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29638
dc.identifier.volume47
dc.identifier.wosWOS:001096172400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Veterinary Pharmacology and Therapeutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectewe
dc.subjectFSH
dc.subjectincreasing dose
dc.subjectletrozole
dc.subjectLH
dc.subjectpharmacokinetics
dc.titlePharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season
dc.typeArticle

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