Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Integration of Enrofloxacin Following Single Oral Administration of Different Doses in Brown Trout (Salmo trutta)

SIMPLE SUMMARY: The pharmacokinetic/pharmacodynamic studies report the use of enrofloxacin at higher doses than 10 mg/kg in fish. Pharmacokinetic data for increasing doses of enrofloxacin can facilitate suggestions regarding the dose for the treatment of infections in brown trout. This study aims to determine single oral pharmacokinetics of enrofloxacin at 10, 20, and 40 mg/kg doses in brown trout and pharmacodynamics against Aeromonas hydrophila and A. sobria. Enrofloxacin exhibited non-linear and dose-disproportional pharmacokinetics. The long action of enrofloxacin following the single oral administration at 10 and 20 mg/kg doses may provide the unique dosage regimen to minimize handling, thereby reducing the cost of administration and stress in brown trout. ABSTRACT: The pharmacokinetic of enrofloxacin was investigated in brown trout (Salmo trutta) following oral administration of 10, 20, and 40 mg/kg doses at 11 ± 1.5 °C. Furthermore, MICs of enrofloxacin against Aeromonas hydrophila and A. sobria were determined. The plasma concentrations of enrofloxacin and ciprofloxacin were determined using HPLC–UV and analyzed by non-compartmental method. Following oral administration at dose of 10 mg/kg, total clearance (CL/F), area under the concentration–time curve (AUC(0−)(∞)) and peak plasma concentrations (C(max)) were 41.32 mL/h/kg, 242.02 h*μg/mL and 4.63 μg/mL, respectively. When compared to 10 mg/kg dose, the dose-normalized AUC(0–)(∞) and C(max) were increased by 56.30% and 30.08%, respectively, while CL/F decreased by 38.4% at 40 mg/kg dose, suggesting the non-linearity. Ciprofloxacin was not detected in the all of plasma samples. The MIC values of enrofloxacin were ranged 0.0625–4 μg/mL for A. hydrophila and 0.0625–2 μg/mL for A. sobria. The oral administration of enrofloxacin at 10 (for 192 h) and 20 (for 240 h) mg/kg doses provided the AUC of enrofloxacin equal to 1.23 and 1.96-fold MICs, respectively, for A. hydrophila and A. sobria with the MIC(90) values of 1 µg/mL. However, further researches are needed on the PK/PD study of enrofloxacin for the successful treatment of infections caused by A. hydrophila and A. sobria in brown trout.