Flumequine comparative pharmacokinetics of oral gavage and pulsed administration in turkey

Flumequine (FLU) is a 1st generation quinolone still used in food-producing species to control infection caused by various Gram-negative bacteria. FLU is employed in several animal species, including avian species and turkeys, due to its relative low cost and good tolerability. In avian species the mass medication via drinking water is the most common method of administration and in clinical practice, a 10 h pulsed medication is frequently adopted. FLU was orally administered to healthy turkey via gavage as a single bolus and via 10 h pulsed medicated water for 5 consecutive days at the doses of 15 mg/kg. Blood samples were taken between 0.25 and 24 h for the bolus administration, and between 1 and 24 h at the 1st and 5th day of administration for the pulsed medicated water. FLU serum concentrations were determined by a validated LC/MS/MS method. Pharmacokinetic data were analyzed using a non-compartmental method method (WinNonLin 6.1). For the bolus FLU, mean peak serum concentration (Cmax 10.76±1.5µg/mL) were achieved at about 2 hours postdose (Tmax 1.88±0.35 h) and mean AUC(0-24) and t1/2el were 76.14±7.69 hr.µg/mL and 4.77±1.48 h, respectively. For the pulsed administration at day 1 and 5 the FLU Cmax were 3.05±0.36 and 4.01±1.3 µg/mL, respectively, Tmax 5.75±2.71 and 6±1.6 h, respectively, AUC(0-24) 33.46±4.65 and 51.54±14.87 hr.µg/mL, respectively and t1/2el 5.31±1.72 and 6.39±1.18 h. The bolus administration is not practicable in turkeys breeding, despite the higher Cmax and AUC attained. The administration with 10 h pulsed medicated water for 5 day caused an AUC increase at day 5. due to drug accumulation. FLU administered to turkeys with 10 h pulsed medicated water for 5 day did not reach serum concentrations comparable to those obtained after bolus. The authorized EU dosage of 15 mg/kg could be ineffective to reach adequate drug serum concentrations even after 5 days when pulsed medicated water is adopted for mass treatment. Thus it could limit the effectiveness of the antimicrobial treatment and may contribute to the selection of resistant micro-organisms.