Scopus
YÖKSİS Eşleşti
Pharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season
Journal of Veterinary Pharmacology and Therapeutics · Mayıs 2024
YÖKSİS Kayıtları
Pharmacokinetics of letrozole and effects of its increasing doses on gonadotropins in ewes during the breeding season.
Journal of veterinary pharmacology and therapeutics · 2024 SCI-Expanded
PROFESÖR KAMİL ÜNEY →
Makale Bilgileri
DergiJournal of Veterinary Pharmacology and Therapeutics
Yayın TarihiMayıs 2024
Cilt / Sayfa47 · 193-201
Scopus ID2-s2.0-85175726738
Özet
Letrozole 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 (t1/2ʎz) 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 (ClT) 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 (C0.083h) plasma concentration values between dose groups. The decreased ClT, prolonged t1/2ʎz, 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.
Yazarlar (7)
1
M. B. Kivrak
2
Orhan Corum
ORCID: 0000-0003-3168-2510
3
Murat Yuksel
ORCID: 0000-0001-6634-0559
4
Erdinc Turk
ORCID: 0000-0003-1735-1774
5
D. Durna Corum
6
Ibrahim Ozan Tekeli
ORCID: 0000-0002-6845-2279
7
Kamil Üney
ORCID: 0000-0002-8674-4873
Anahtar Kelimeler
ewe
FSH
increasing dose
letrozole
LH
pharmacokinetics
Kurumlar
Selçuk Üniversitesi
Selçuklu Turkey
University of Hatay Mustafa Kemal
Hatay Turkey
University of Sivas Cumhuriyet
Sivas Turkey