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Effect of dietary fat on oral bioavailability of tepoxalin in dogs
Author(s) -
HOMER L. M.,
CLARKE C. R.,
WEINGARTEN A. J.
Publication year - 2005
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2005.00644.x
Subject(s) - bioavailability , metabolite , pharmacokinetics , chemistry , oral administration , primary metabolite , pharmacology , urine , food science , chromatography , medicine , biochemistry
A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low‐fat or high‐fat commercial diet. Using a cross‐over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low‐fat, or high‐fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (±SD) half‐life of elimination ( t 1/2( β ) ) was 2.45 ± 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first‐pass effect. Mean (±SD) peak concentrations of tepoxalin were significantly higher after feeding of low‐fat (1.08 ± 0.37 μ g/mL) and high‐fat (1.19 ± 0.29 μ g/mL) diets than in fasted dogs (0.53 ± 0.20 μ g/mL), suggesting that feeding improves oral bioavailability.