PII-150 - POPULATION PHARMACOKINETICS OF ENROFLOXACIN AND FLORFENICOL IN THE GIANT DANIO (DEVARIO AEQUIPINNATUS) FOLLOWING ORAL AND BATH ADMINISTRATION

J. Zhou¹, B. S. Vorbach², Y. Lang¹, Y. Zhang¹, J. B. Bulitta¹, R. P. E. Yanong¹; ¹University of Florida, ²Resident, Aquatic Animal Health.

Background: The giant danio is a cyprinid species closely related to the zebra danio, and they share similar natural environments and husbandry requirements. However, the giant danio is a larger species of fish, which makes it a suitable substitute for the zebra danio in pharmacokinetic (PK) studies. This study aims to determine the population PK of enrofloxacin and florfenicol using oral and bath dosing in giant danios. Monte Carlo simulations (MCS) were used to predict unbound drug exposures and calculate the probability of PK/pharmacodynamic (PD) target attainment.

Methods: Oral florfenicol was dosed at 60 mg/kg and oral enrofloxacin at 8 mg/kg. For bath dosing, fish remained in a bath containing 8 or 10 mg/L enrofloxacin for 5 hours. Each fish contributed one blood and one muscle tissue sample. Drug concentrations of enrofloxacin and florfenicol in blood and muscle homogenate were determined by UPLC-MS/MS. Population PK modeling was performed in the S-ADAPT software (importance sampling algorithm) and MCS in Berkeley Madonna using the fAUC0-24/MIC as PK/PD targets.

Results: Florfenicol and enrofloxacin could be quantified in both matrices over 48 h. Florfenicol was absorbed rapidly (half-life: 16.3 min, 20% between subject variability, BSV) and had an apparent total clearance of 1.89 mL/h (21% BSV). Enrofloxacin was rapidly absorbed orally (half-life: 14.0 min, 80% BSV) and its apparent total clearance was 1.17 mL/h (34% BSV). At an oral dose of 8 mg/kg, enrofloxacin achieved peak concentrations of approximately 3 mg/L in blood and 3 to 4 µg/g in muscle tissue homogenate. After bath dosing for 5 h at an enrofloxacin concentration of 10 mg/L, peak concentrations were approximately 0.3 to 0.6 mg/L in blood and 0.4 to 1.0 µg/g in muscle tissue homogenate. The ratio of drug exposures in muscle tissue and blood was 0.782 (19% BSV) for florfenicol and 1.61 (33% BSV) for enrofloxacin. MCS predicted that oral administration of enrofloxacin and florfenicol could attain unbound drug exposures that are sufficient to treat common freshwater bacterial infections.

Conclusion: This study showed that enrofloxacin and florfenicol achieved promising drug exposures in blood and muscle tissue of giant danio for bacterial pathogens relevant to fish. Thereby, this work supported veterinary professionals to treat giant danio and related fish effectively.