Pharmacokinetics, pharmacokinetic-pharmacodynamic relationship, and withdrawal period of amoxicillin sodium in olive flounder (Paralichthys olivaceus)

1. The pharmacokinetics (PK) and withdrawal period of amoxicillin sodium in olive flounder and its activity against pathogenic bacteria of olive flounder were investigated.2. Intramuscular administration (12.5 or 125 mg/kg, n = 160) and HPLC analysis of sera were used.3. Rapid absorption (T_max 2.6 and 2.2 h), prolonged action (terminal half-life, 15.52 and 10.42 h; MRT, 18.79 and 14.44 h), and dose-proportional exposure (AUC0-_∞, 273.69 and 2755.37 h. g/ml) were observed after 12.5 and 125 mg/kg doses.4. The withdrawal period of amoxicillin sodium from muscle plus skin of olive flounder (n =40, water temperature, 23 °C) was 12 d (276 degree days).5. Amoxicillin sodium had small MICs against Streptococcus iniae (0.008-0.06 g/ml) and Streptococcus parauberis (0.03-1.0 g/ml), whereas higher concentrations were required to inhibit Edwardsiella tarda isolates (0.06-16 g/ml).6. While large AUC0-24 _h/MIC₉₀ and C_max/MIC₉₀ ratios were obtained for S. iniae and S. parauberis, with drug concentrations in serum greater than MICs for the entire dosing interval (T > MIC₉₀ of 100%), the lower dose (12.5 mg/kg) could not achieve target values of the PK-pharmacodynamic (PD) indices for E. tarda isolates, suggesting the need for higher doses to combat pathogenic bacteria with large MICs.