Details

Autor(en) / Beteiligte

• Ueno, Ryuji
• Okada, Yasushi
• Tatsuno, Takuya

Titel

Pharmacokinetics and metabolism of miloxacin in cultured eel

Ist Teil von

• Aquaculture, 2001-02, Vol.193 (1), p.11-24

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2001

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Miloxacin (5,8-dihydro-5-methoxy-8-oxo-2 H-1,3-dioxolo-[4,5- g]quinoline-7-carboxylic acid) is a synthetic antibacterial agent and is regulated in conformity with the Pharmaceutical Law in Japan. The pharmacokinetics and metabolism of miloxacin after intravascular and oral administration in cultured eel ( Anguilla japonica) were examined by using our high-performance liquid chromatography (HPLC) system, which was developed as a reliable and precise method for simultaneous determination of miloxacin and its metabolite in this study. The kinetics of miloxacin was described by a two-compartment model after intravascular administration. The distribution half-life ( T 1/2 α =0.86 h) of miloxacin was shorter than the elimination half-life ( T 1/2 β =34.7 h). The kinetics of orally administered miloxacin was fitted to a one-compartment model. Miloxacin was assimilated quickly ( T a1/2=3.5 h) and cleared slowly ( T 1/2=34.7 h) after oral dosing. The bioavailability was calculated to be 87.9%. The tissue levels of miloxacin reached their peak levels within 1 day after oral administration. At their highest levels, the concentrations of miloxacin were observed in the order of kidney>muscle>liver. Miloxacin, its main metabolite 5,8-dihydro-8-oxo-2 H-1,3-dioxolo-[4,5- g]quinoline-7-carboxylic acid (M-1) and the glucuronic acid conjugate of miloxacin and M-1 were detected, and a large amount of M-1 was still observed in bile at 20 days post dosing. As an application of pharmacokinetics, we attempted to evaluate the Japanese dosage regimens of miloxacin in cultured eel. A curve for predicting miloxacin levels was obtained by a computerized calculation, using various pharmacokinetics parameters that were experimentally determined. The curve was coincident with drug levels during the actual multiple oral dosing (60 mg/kg body weight) in this experiment. The serum levels of miloxacin were maintained above the MIC (for Edwardsiella tarda, 0.1 μg/ml). However, this seems to be a considerably excessive dosing because of the high value of the average steady-state serum concentration (Css: 55.4 μg/ml).