Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Black Rockfish (Sebastes schlegelii) Following a Single Oral Administration at Two Water Temperatures.

Abstract

This study investigated the pharmacokinetics of enrofloxacin (ENR) and its primary metabolite, ciprofloxacin (CIP), in black rockfish (Sebastes schlegelii) following a single oral administration of ENR (10 mg/kg) under two water temperature conditions (13°C and 22°C). Serum samples were collected up to 168 h post-dosing and analyzed using a validated HPLC-MS/MS method. Contrary to conventional expectations, ENR absorption was delayed and elimination was slower at 22°C compared to 13°C, while the plasma concentrations of CIP were higher at the elevated temperature. The elimination half-life of ENR increased from 27.38 h at 13°C to 42.01 h at 22°C, despite enhanced hepatic metabolism. These findings suggest that the primary route of ENR elimination may shift from passive diffusion via the gills at lower temperatures to hepatic metabolism at higher temperatures, likely due to functional impairment of the gill tissues under thermal stress. Notably, the AUC values of ENR remained comparable between the two groups, indicating consistent drug exposure despite differing pharmacokinetic dynamics. PK/PD analysis revealed that single-dose administration may not achieve optimal therapeutic indices (AUC_0-24h/MIC ≥ 125, C_max/MIC ≥ 10) against certain bacterial pathogens, underscoring the need for repeated dosing. Overall, this study provides novel insights into the temperature-modulated pharmacokinetics of ENR and highlights the importance of temperature-specific dosing strategies for effective antibiotic therapy in aquaculture species like black rockfish.