[PMID]: | 28697876 |
[Au] Autor: | Mendoza FJ; Serrano-Rodriguez JM; Buzon-Cuevas A; Perez-Ecija A |
[Ad] Endereço: | Department of Animal Medicine and Surgery, University of Cordoba, Campus Rabanales, Cordoba 14104, Spain. Electronic address: fjmendoza@uco.es. |
[Ti] Título: | Pharmacokinetics of the anti-androgenic drug flutamide in healthy stallions. |
[So] Source: | Vet J;224:50-54, 2017 Jun. |
[Is] ISSN: | 1532-2971 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | Alternatives to surgical castration are necessary for controlling the sexual behaviour of stallions with breeding potential in training and competition. Flutamide is a potent selective non-steroidal androgen receptor competitive antagonist that has been used in human beings as an anti-androgenic drug. In this study, the pharmacokinetics and bioavailability of flutamide and its main active metabolite, 2-hydroflutamide, were determined in seven healthy mature stallions. Single doses of flutamide (1mg/kg intravenously, 1mg/kg orally in fasted horses, 5mg/kg orally in fasted horses and 5mg/kg orally in fed horses) were administered randomly at intervals of 2 weeks. All horses had full physical examinations and blood samples were collected for pharmacokinetics, complete blood counts and biochemistry before and after drug administration. Administration of flutamide did not result in any abnormalities on physical examination or in blood parameters. After intravenous administration of flutamide, the volume of distribution was 0.83L/kg and clearance was 1.20L/h/kg. Flutamide and its metabolite had high protein binding values (93-97%). After oral administration, flutamide was rapidly transformed to 2-hydroxyflutamide, with areas under the concentration-time curve ratios of metabolite:drug ∼7. Oral bioavailability was 6.63% after 1mg/kg flutamide in fasted horses, 6.50% after 5mg/kg flutamide in fasted horses and 6.95% after 5mg/kg in fed horses. Half lives of flutamide were close to 1h after intravenous administration and 2h after oral administration. Half lives of 2-hydroxyflutamide were 4.79-6.84h for all routes and doses. After oral administration, oral flutamide reached plasma concentrations that could be effective as an anti-androgenic agent in horses, but further studies are needed to determine whether flutamide has clinical value as an alternative to castration for controlling sexual behaviour in stallions. |
[Mh] Termos MeSH primário: |
Antagonistas de Androgênios Flutamida/farmacocinética Cavalos/metabolismo
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[Mh] Termos MeSH secundário: |
Administração Oral Animais Área Sob a Curva Disponibilidade Biológica Jejum Flutamida/administração & dosagem Flutamida/análogos & derivados Flutamida/sangue Meia-Vida Injeções Intravenosas/veterinária Masculino
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[Pt] Tipo de publicação: | COMPARATIVE STUDY; JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Androgen Antagonists); 31D90UKP5Y (hydroxyflutamide); 76W6J0943E (Flutamide) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171106 |
[Lr] Data última revisão:
| 171106 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170713 |
[St] Status: | MEDLINE |
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