Pharmacokinetics of ibafloxacin in healthy cats

Abstract

The pharmacokinetics of ibafloxacin following single and repeated administration of an oral gel formulation and the effect of food intake were investigated in cats. Ibafloxacin is a chiral fluoroquinolone available for clinical use as a racemic mixture of the R- and S-enantiomers. Plasma concentrations of ibafloxacin and its metabolites were determined using microbiological, LC-MS-MS and enantioselective capillary zone electrophoresis assays. Ibafloxacin was absorbed rapidly [time of maximum concentration (tmax) 2-3 h], reaching a mean maximum concentration (Cmax) of approximately 2.1 and 1.6 microg/mL for R- and S-ibafloxacin, respectively, following a single oral administration of the racemate at 15 mg/kg. Once absorbed, ibafloxacin was metabolized to 7-hydroxy-ibafloxacin and mainly to 8-hydroxy-ibafloxacin. Following repeated oral administration, significant increases in Cmax and AUC of ibafloxacin and its less active metabolites (racemic or enantiomers) were observed between the first and the tenth day of treatment. This twofold exposure increase in concentrations of ibafloxacin and its metabolites may contribute additionally to the efficacy of this drug in the treatment of feline bacterial infections. Single and repeated doses of ibafloxacin were well tolerated by cats. Food promoted the absorption of ibafloxacin, doubling Cmax and increasing AUC and slightly delaying tmax. High concentrations of the metabolites, mainly 8-hydroxy- and 7-hydroxy-ibafloxacin were excreted in urine, either unchanged or as glucurono-conjugates.