Kinetic aspects of flumequine after repeated intramuscular administration in lactating cows

Flumequine (FLU) is a 2nd generation quinolone commonly used in food-producing species to control infection caused by various Gram-negative bacteria. Despite the availability of newer fluoroquinolones, FLU is still employed in several animal species mainly due to its relative low cost and good tolerability. FLU was intramuscularly administered to healthy lactating cows, with a priming dose of 6 mg.kg-1 b.w. followed by 5 maintenance doses of 3 mg.kg-1 every 12 h. Blood samples were taken between 0.5 and 84 h, while milk samples were collected every 12 h during treatments and for the 10 milkings after. FLU serum and milk concentrations were determined by a validated HPLC method. FLU reached mean peak serum concentration (Cmax 0.70±0.06 µg.ml-1) at about 4 hours (Tmax 3.32±0.65 h) and was still detected 84 h after treatments (mean 0.14±0.03 µg.ml-1). A mono-compartmental analysis was carried out on serum data (WinNonLin 5.0.1): after repeated administration mean AUC(0-∞) and t1/2el were 11.90±1.11 (hr*µg.ml-1) and 9.14±0.53 (h), respectively. Milk concentration were above LOQ (25 µg.kg-1) only after priming dose (mean 40.42±13.69 µg.kg-1). During maintenance doses FLU decreased at values close to LOQ and rapidly disappeared after last treatment (60 h). The very low milk concentrations did not allow to perform kinetic analysis. Serum concentrations after IM administrations can be considered efficacious against systemic infections during acute mastitis; nevertheless, FLU concentrations in milk seem too low to assure therapeutic effectiveness towards udder Gram-negative infections.