Pharmacokinetics and tissue residues of marbofloxacin in crucian carp (Carassius auratus) after oral administration.

摘要

Pharmacokinetics and residue elimination of marbofloxacin (MBF) were studied in crucian carp (Carassius auratus, 250+or-30 g) kept at two water temperatures of 15 and 25 degrees C. Marbofloxacin concentrations in plasma and tissues were analysed by means of high-performance liquid chromatography using an ultraviolet detector. The limits of detection were 0.02 micro g mL-1, 0.02 micro g g-1, 0.025 micro g g-1, 0.02 micro g g-1 and 0.025 micro g g-1 in plasma and muscle, skin, liver and kidney respectively. Fish were administered orally at a single dosage of 10 mg kg-1 body weight in the PK group. The data were fitted to two-compartment open models at both temperatures. At 15 degrees C, the absorption half-life (t_1/2Ka) and distribution half-life (t_{1/2 alpha} ) of the drug were 0.36 and 4.48 h respectively. The corresponding values at 25 degrees C were 0.23 and 0.87 h respectively. The elimination half-life (t_{1/2 beta} ) was 50.75 h at 15 degrees C and 25.05 h at 25 degrees C. The maximum MBF concentration (C_max) differed little between 15 (6.43 micro g mL-1) and 25 degrees C (8.36 micro g mL-1). The time to peak concentration was 1.74 h at 15 degrees C and 0.78 h at 25 degrees C. The apparent volume of distribution (V_d/F) of MBF was estimated to be 1.36 and 0.87 L kg-1 at 15 and 25 degrees C respectively. The area under the concentration-time curve (AUC) was 301.80 micro g mL-1 h at 15 degrees C and 182.80 micro g mL-1 h at 25 degrees C. The total clearance of MBF was computed as 0.03 and 0.05 L h-1 kg-1 at 15 and 25 degrees C respectively. After repeated oral administration at a dosage of 10 mg kg-1 body weight per day for 3 days, the results showed that the elimination half-lives (t_1/2Ke) of MBF from all tissues at 15 degrees C were longer than that at 25 degrees C. Therefore, water temperature is an important factor to be considered when deciding a reasonable withdrawal time.