ANTIINFECTANTS: Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 28; no. 5; pp. 425 - 431
• Main Authors: Davis, J L, Salmon, J H, Papich, M G
• Format: Journal Article
• Language: English
• Published: 01.10.2005
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2005.00683.x

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t sub(1/2)) of 2.02 h and volume of distribution [V sub(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C sub(max)) was 3.47 mu g/mL and an apparent half-life (t sub(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC sub(ISF):AUC sub(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t sub(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 plus or minus 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 mu g/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC less than or equal to 0.5 mu g/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.