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

Basit Öğe Kaydı
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.accessioned2024-09-18T20:19:55Z
dc.date.available2024-09-18T20:19:55Z
dc.date.issued2024
dc.departmentHatay Mustafa Kemal Üniversitesien_US
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.en_US
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 Kemalen_US
dc.description.sponsorshipThis study was supported by the Coordination of Scientific Research Projects, University of Hatay Mustafa Kemal, Turkiye (Project No. 20.M.031).en_US
dc.identifier.doi10.1111/jvp.13414
dc.identifier.endpage201en_US
dc.identifier.issn0140-7783
dc.identifier.issn1365-2885
dc.identifier.issue3en_US
dc.identifier.pmid37920137en_US
dc.identifier.startpage193en_US
dc.identifier.urihttps://doi.org/10.1111/jvp.13414
dc.identifier.urihttps://hdl.handle.net/20.500.12483/9956
dc.identifier.volume47en_US
dc.identifier.wosWOS:001096172400001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofJournal of Veterinary Pharmacology and Therapeuticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjecteween_US
dc.subjectFSHen_US
dc.subjectincreasing doseen_US
dc.subjectletrozoleen_US
dc.subjectLHen_US
dc.subjectpharmacokineticsen_US
dc.titlePharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding seasonen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu