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Robenacoxib pharmacokinetics in sheep following oral, subcutaneous, and intravenous administration

The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX‐2 selective non‐steroidal anti‐inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three‐phase parallel study desig...

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Detalles Bibliográficos
Autores principales: Fadel, Charbel, Łebkowska‐Wieruszewska, Beata, Sartini, Irene, Lisowski, Andrzej, Poapolathep, Amnart, Giorgi, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796919/
https://www.ncbi.nlm.nih.gov/pubmed/35899473
http://dx.doi.org/10.1111/jvp.13089
Descripción
Sumario:The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX‐2 selective non‐steroidal anti‐inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three‐phase parallel study design with a washout period of 4 weeks, in which sheep received a 4 mg/kg SC dose in phase 1, a 4 mg/kg PO administration in phase 2, and a 2 mg/kg IV administration in phase 3. Plasma RX concentrations were measured over a 48 h period for each treatment using HPLC coupled to a UV multiple wavelength detector, and the PK parameters were estimated using a non‐compartmental method. Following IV administration, terminal elimination half‐life, volume of distribution at steady state, and total clearance were 2.64 h, 0.077 L/kg, and 0.056 L/h kg, respectively. The mean peak plasma concentrations following SC and PO administrations were 7.04 and 3.01 μg/mL, respectively. The mean bioavailability following SC and PO administrations were 45.98% and 16.58%, respectively. The SC route may be proposed for use in sheep. However, the multi‐dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in sheep.