DAO 54:35-41 (2003)  -  doi:10.3354/dao054035

ABSTRACT: The present study investigated the kinetic profile of flumequine (FLU) in gilthead sea bream Sparus aurata (170 g) held at 19°C and evaluated its in vitro efficacy against important bacterial diseases in Mediterranean mariculture. Following a single intravascular injection (10 mg kg^-1 fish), the distribution half-life (t_x1/2α) and the half-life of the terminal phase of elimination (t_{1/2 γ}) of the drug were 0.2 and 30 h respectively. Tissue penetration of FLU was low, since both the apparent distribution volume of the drug at steady-state (V_d(ss)) and the apparent volume of the central compartment (V_c) were small (0.57 and 0.15 l kg^-1). The mean residence time (MRT) was short (11 h) and the total clearance (CL_T) of the drug was slow (0.05 l kg^-1 h^-1). Following oral administration (20 mg kg¹), the bioavailability (F %) of FLU was 29% and the maximum plasma concentration was 1.7 µg ml^-1. The minimum inhibitory concentration (MIC) of the drug in distilled water supplemented with 2% NaCl against Vibrio anguillarum Serotype 1b, Photobacterium damsela ssp. piscicida, V. alginolyticus, V. damsela and V. fluvialis was 0.15, 0.3, 1.2, 0.019 and 0.15 µg ml^-1 respectively. The addition however of 10 mM Ca²⁺ and 55 mM Mg²⁺ to the medium resulted in an 8- to >120-fold reduction in FLU activity. The results indicate that FLU has an adequate kinetic profile in gilthead sea bream and that marine cations induce a significant impact on the activity of FLU, rendering its use against bacterial pathogens questionable.

KEY WORDS: Flumequine · Gilthead sea bream · Pharmacokinetics · Bioavailability · Minimum inhibitory concentration · Mediterranean mariculture