Population Pharmacokinetics of Sarafloxacin in Yellow River Carp (Cyprinus carpio Haematopterus) After One Single Oral Dose.

Abstract

The objective of this study was to investigate the population pharmacokinetics of sarafloxacin following a single oral administration at a dose of 20 mg/kg body weight (BW) in Yellow River carp (Cyprinus carpio haematopterus) reared at 24°C, and to provide a scientific basis for its rational use in aquaculture. Blood samples were collected from the tail vein of six fish at each predetermined time point: 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 46, 48, 92, 96, 120, and 144 h post-administration, using a sparse sampling design. Blood was collected only four times per fish, and six fish were sampled at each time point. Plasma concentrations of sarafloxacin were measured using high-performance liquid chromatography (HPLC), and the drug remained quantifiable in plasma up to 120 h post-administration. Population pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling to characterize both the typical population parameters (fixed effects) and inter-individual variability (random effects). Covariate and covariance models were incorporated to account for variability and improve model predictability under sparse sampling conditions. The final population model estimated typical values (tv) and inter-individual coefficients of variation (CV%) for the absorption rate constant (tvK_a), apparent volume of distribution (tvV), and clearance (tvCL) as 14.889 h^-1 (CV: 3.04%), 31.573 L/kg (CV: 0.39%), and 2.885 L/h/kg (CV: 0.38%), respectively. Based on the calculated AUC/MIC or C_max/MIC ratios, the current oral dosing regimen of 20 mg/kg BW appears to be effective against pathogens with MIC values below 0.05 μg/mL.