1. Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration.
- Author
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Kleinhenz MD, Odland C, Williams TE, Zhang Y, Fitzgerald AH, Sidhu PK, Wulf LW, and Coetzee JF
- Subjects
- 4-Butyrolactone administration & dosage, 4-Butyrolactone pharmacokinetics, Administration, Oral, Analgesics administration & dosage, Animals, Area Under Curve, Biological Availability, Cross-Over Studies, Female, Half-Life, Sulfones administration & dosage, 4-Butyrolactone analogs & derivatives, Analgesics pharmacokinetics, Sulfones pharmacokinetics, Swine metabolism
- Abstract
The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (T
max ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib., (© 2020 John Wiley & Sons Ltd.)- Published
- 2020
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