Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats

The pharmacokinetics of single intravenous and intramuscular administrations and milk antimicrobial equivalent activity of enrofloxacin at a dose of 5 mg per kilogram body weight were studied in clinically healthy lactating goats which were either not treated or had received 7.5 mg per kilogram body weight of albendazole orally. The concentrations of enrofloxacin in serum and milk were determined using microbiological assay. Following intravenous injection, enrofloxacin antimicrobial equivalent activity versus time data in serum was described by a two-compartmental open model. Albendazole treatment significantly decreased the elimination half-life (t(1/2beta)) (P greater than or equal to 0.05) and the mean residence time (MRT) (P greater than or equal to 0.05), whereas, the rate of enrofloxacin return to central compartment from peripheral tissue (K-21) was significantly increased (P greater than or equal to 0.01). In contrast, the volumes of distribution V-d(area) and V-d(SS) were significantly decreased (P greater than or equal to 0.01 and P greater than or equal to 0.05, respectively) in albendazole-treated goats. After intramuscular injection, enrofloxacin was rapidly absorbed in control and albendazole-treated lactating goats with absorption half-lives (t(1/2ab)) 0.43 and 0.39 h, respectively. The mean peaks of serum concentration (C-max) were 0.68 and 0.65 mcg ml(-1) attained at (t(max)) 1.08 and 1.12 h, before and after albendazole dosing, respectively. The elimination half-life (t(1/2el)) and (MRT) following intramuscular injections were also shorter in the albendazole-treated lactating goats. The systemic bioavailability of enrofloxacin was significantly decreased from 110.16 to 84.38% in albendazole-treated lactating goats. Concomitant administration of albendazole with enrofloxacin resulted in significant alterations in the disposition kinetic of enrofloxacin and significant decrease in enrofloxacin concentrations in milk. Consequently, the interaction between albendazole and enrofloxacin could be of clinical significance and may require monitoring and adjustment of enrofloxacin dosage. (C) 2003 Elsevier Ltd. All rights reserved.