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.
1. The pharmacokinetics of oxolinic acid have been studied in 500 g turbot (Scophthalmus maximus). The fish were kept in seawater at 16 degrees C with a 15 h/9 h photoperiod. Oxolinic acid was administered orally via a stomach tube at a single dose of 10 mg/kg of body weight. Serum concentrations of oxolinic acid were determined by a (HPLC) using liquid phase extraction with an internal standard and a fluorescence detection. 2. The pharmacokinetic process was not significantly sex-influenced. The short elimination phase of the oxolinic acid in turbot after oral administration was similar to the elimination after intravascular administration. The serum concentration profile of oxolinic acid was better described by a discontinuous absorption model than by compartment models using continuous absorption processes. The absorption of oxolinic acid in turbot was characterized by two distinct phases after a lag time of about 2 h. A time (Tmax) of 12 h was necessary to reach the peak serum concentration (Cmax) of 1.41 microg/ml. The oral bioavailability was 27.9%. 3. Based on the minimum inhibitory concentration for susceptible strains, and especially Vibrio anguillarum, the oxolinic acid could be effective in turbot after an oral treatment of 10 mg/kg/day.
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