The present study examined the pharmacokinetics and bioavailability of oxytetracycline (OTC) in vannamei shrimp (Penaeus vannamei) after intra-sinus (10 mg/kg) and oral (10 and 50 mg/kg) administration and also investigated the net changes of OTC residues in the shrimp after the thermal, acid and alkaline processing methods. The hemolymph concentrations of OTC after intra-sinus dosing were best described by a twocompartment open model. The oral bioavailability was found to be 48.2 and 43.6% at doses of 10 and 50 mg OTC/kg, respectively. The peak hemolymph concentrations after 10 and 50 mg OTC/kg doses were 3.37 and 17.4 lg/ml; the times to peak hemolymph concentrations were 7 and 10 h. The elimination half-lives were found to be 15.0 and 11.5 h for the low and high dose, respectively. The residual OTC was rapidly eliminated from muscle with the elimination half-life value of 19.4 and 15.4 h, respectively, for the groups treated with doses of 10 and 50 mg/kg. The residual OTC levels in the muscle fell below the MRL (0.2 lg/g) at 72 and 96-h post-dosing at dose levels of 10 or 50 mg/kg, respectively. Residual OTC levels in muscle and shell were approximately 20-50% lower in the thermal treatment such as boiling, baking and frying. By the acid treatment, OTC residues were reduced to [80%, while those were reduced to around 30% by alkaline treatment.
Tissue distribution and residue depletion of oxytetracycline (OTC) and oxolinic acid (OA) were studied in the kuruma prawn (Penaeus japonicus). The prawn were kept in tanks with recirculated artificial seawater at a salinity of 22ῐ23̮. The water temperature was maintained at 25̮. The average body weight was 22.94.9 g for OTC and 22.53.6 g for OA. The drug was mixed with the diet and orally administered through a catheter to the prawn. The doses of OTC and OA, respectively, were 50 mg/kg body weight. At each sample time, four prawns were sacrificed and tissues were sampled. OTC and OA levels were determined by high-performance liquid chromatography. At the highest levels, the concentrations of OTC were in the order: shell (13.57 mg/g)̮hemolymph (12.20 mg/mL)̮muscle (8.30 mg/g). For OA, the order was: shell (20.74 mg/g)̮hemolymph (7.06 mg/mL)̮muscle (2.05 mg/g). The elimination half-lives of hemolymph and muscle were 44.7 and 46.8 hours for OTC and 55.0 and 107.9 hours for OA, respectively. Residual OTC could not be detected in hemolymph and muscle at 20 days after dosing. Residual OA disappeared from hemolymph and muscle at 25 days after dosing. A 25-day period for OTC and 30-day period for OA could be regarded as the proper withdrawal time established for kuruma prawn by the Pharmaceutical Law in Japan. However, the elimination half-lives of shell for OTC and OA could not be calculated because both drug residues persisted in shell tissues, and the elimination phase was not completed during the experimental period. Residual OTC (14.102.26 mg/g, n̮6) and OA (0.320.06 mg/g, n̮7) were detected in exuviae at 3 days and 4 days after dosing, respectively. Residual OTC was reduced to 50ῐ70̮ in muscle by the usual methods of cooking (boiling, baking at 200̮ and frying at 180̮), whereas reduction levels in shell were only 20ῐ30̮. Residual OA was reduced to 20ῐ30̮ in muscle and shell by the cooking. These results confirm that the cooking procedures could only reduce but not completely eliminate these drug residues in prawn.
This study examined the pharmacokinetics and bioavailability of oxolinic acid (OA) in black tiger shrimp Penaeus monodon Fabricius, in brackish water (salinity 10 g L À 1 ) at 28^29 1C, after intra-sinus (10 mg kg À1 ) and oral (50 mg kg À1 ) administration and also investigated the net changes of OA residues in the shrimp after cooking (boiling, baking and frying). The haemolymph concentrations of OA after intra-sinus dosing were best described by a two-compartment open model. The distribution and elimination half-lives were 0.84 and 17.7 h respectively. The apparent volume of distribution at a steady state and the total body clearance were estimated to be 2061mL kg À1 and 90.1mL kg À1 h À1 respectively. The bioavailability of OA after an oral administration was 7.9%. The peak haemolymph concentration, the time to peak haemolymph concentration and the elimination half-life after oral administration were 4.20 mg mL À1 , 4 h and 19.8 h respectively. Oxolinic acid muscle and shell levels increased to a maximum (muscle 1.76 mg g À1 and shell 8.17 mg g À1 ) at 4 h post administration and then decreased with the elimination half-life value of 20.2 and 21.9 h respectively. Residual OA in muscle and shell was reduced by 20^30% by each cooking procedure examined.
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