PK/PD of flumequine in pigs after intravenous and intramuscular administration

Flumequine is a second generation antibacterial quinolone derivative, developed solely for use in animals. The drug is widely employed in food-producing species (ruminants, pigs, birds, fish) to control infections caused by a range of Gram-negative bacteria and is commonly administered at doses of 5-6 up to 15 mg.kg-1 b.w. every 12 hours. The kinetic behavior of flumequine has been studied in many animal species but not in pigs and dosing in these animals are to some extent empirical as it is based on results obtained in other animals. In this study the pharmacokinetics and intramuscular bioavailability of flumequine (15 mg.kg-1) in pigs were determined and the findings related to published minimal inhibitory concentrations (MICs) for susceptible bacteria of animal origin and to experimentally determined MICs for susceptible strains of porcine origin. We determined MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and Bordetella spp isolated from infected pigs in the Forlì area of Italy; Pasteurella multocida strains were particularly sensitive (MIC90 = 0.5 µg.mL-1). After intravenous injection flumequine was slowly distributed and eliminated (t½11.40±0.16 h and t½26.35±1.69 h). The distribution volume at steady state (Vdss) was 752.59±84.03 mL.kg-1 and clearance (ClB) was 237.19±17.88 mL.kg-1.h-1. The bioavailability was about 85%. The PK/PD analysis allows to conclude that flumequine could be effective in controlling respiratory infections caused by Pasteurella multocida, while its effectiveness against gastrointestinal infections caused by Salmonella typhimurium and Escherichia coli may be impaired by the emergence of less sensitive or resistant strains.