The pharmacokinetics of oxolinic acid was studied in sea-bass (Dicentrarchus labrax). The fish were kept in seawater at 15.2 degrees C with a 12 h/12 h photoperiod. Oxolinic acid was injected in the caudal vein of anaesthetized sea-bass in a single rapid intravascular administration at a dose of 10 mg/kg of body weight. Plasma concentrations of oxolinic acid were determined using two analytical methods, a classic plate diffusion bioassay using Escherichia coli and a high performance liquid chromatography (HPLC) using solid phase extraction with an internal standard and a U.V. detection. The mean recoveries were 99.6% and 110.8% and determination limits were 0.04 microg/mL and 0.02 microg/mL, for the bioassay and the HPLC respectively. Compared to other fish species, the oxolinic acid was rapidly (absorption half life, t(a1/2) = 0.69 h) distributed to body tissues outside the blood volume (volume of central compartment, Vc = 0.4 L/kg) and presented a large volume of distribution (Vdss = 2.55 L/kg). Considering its disappearance from the central compartment (rate constant: central-eliminated, k10 = 0.16 h[-1]) and its total body clearance (Cl[t] = 0.066 L/kg x h), the elimination phase of the oxolinic acid in sea-bass was shorter than in trout kept in freshwater, and longer than in salmon in seawater. Consequently, the area under the concentration-time curve (AUC = 157 microg x h/mL) and the mean residence time (MRT = 42 h) were relatively low and short, respectively.

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A simple high performance liquid chromatographic method for the determination of oxolinic acid, a chemotherapeutic agent, in turbot serum has been developed. Nalidixic acid was used as an internal standard. The drugs were separated by using a 5 pm Supelcosil ABZ+Plus@ reversed phase cartridge, a mobile phase of acetonitrile, tetrahydrofuran and 0.00 1 M orthophosphoric acid solution (22:10:68 vh). pH 3.4 with a fluorescence detection. The sample clean-up was reduced to the use of precipitating agents and centrifugations because the solid-phase extraction procedure was not suited to the analysis of oxolinic acid in turbot serum. 591 592 POULIQUEN ET AL.Linearity and precision were checked over the concentration range 0.020-2.500 pg/mL,. Limits of detection and determination were respectively 0.005 and 0.015 pg/mL. Recoveries of oxolinic acid from turbot serum were between 103.89 and 110.71 %.