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Diseases of Aquatic Organisms

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

Pharmacokinetics of flumequine and in vitro activity against bacterial pathogens of gilthead sea bream Sparus aurata

George Rigos1,3,*, Athanassios E. Tyrpenou2, Ioannis Nengas1, Maria Yiagnisis1, Maria Koutsodimou1, Maria Alexis1, Gera M. Troisi3,4

1Laboratory of Fish Nutrition and Pathology, National Centre for Marine Research, Aghios Kosmas 16604, Ellinikon, Attiki, Greece
2Department of Residue Research, HPLC Laboratory, Institute of Veterinary Research of Athens, National Agricultural Research Foundation, 25 Neapoleos Street, Agia Paraskevi 15310, Athens, Greece
3School of Life Sciences, Kingston University, Kingston upon Thames KT1 2CC, Surrey, United Kingdom
4Present address: Environmental Monitoring Unit, Department of Mechanical Engineering, Brunel University, Uxbridge UB8 3PH, United Kingdom

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 (tx1/2α) and the half-life of the terminal phase of elimination (t1/2 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 (Vd(ss)) and the apparent volume of the central compartment (Vc) were small (0.57 and 0.15 l kg-1). The mean residence time (MRT) was short (11 h) and the total clearance (CLT) 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

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