Disposition kinetics and bioavailability of doxycycline after parenteral administrations in ewes

Abstract

Doxycycline is a tetracycline, which have been marketed in different species for treating infections caused by susceptible bacteria. There is limited information on the disposition kinetics of this drug in ewes and this antimicrobial may be useful against several sheep pathogens that are common causes of morbidity and economic loss. Therefore, the aim of this work was to establish the pharmacokinetics of doxycycline after intravenous (IV) and extravascular (subcutaneous (SC) and intramuscular (IM)) administrations in this species. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for IV administration and 20 mg/kg for extravascular administrations. Non-compartmental pharmacokinetic methods were used to calculate plasma concentration-time data. The value of apparent volume of distribution (V_z) suggests a moderate distribution of this antibiotic in sheep, with a value of 0.84 L/kg. The maximum concentrations achieved after extravascular administrations (C_max) were similar, with no significant differences between the two routes of administration (IM and SC). However, doxycycline absorption was slower after SC administration than after IM administration, taking twice as long to reach maximum plasma concentration (t_max). Bioavailabilities after extravascular routes of administration were low and after IM administration doxycycline caused lameness in all animals. Therefore, the SC administration showed a better profile with respect to pharmacokinetic properties and safety. Future studies on the susceptibility of isolated sheep pathogens to doxycycline are needed to establish appropriate dosing regimens.