Salinity-dependent pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus) and its implication in optimal dosing regimen

Nile tilapia has been cultured in a wide salinity range, from freshwater to up to 15 ppt brackish water due to its euryhaline characteristics. As salinity profoundly affects the physiology of freshwater and seawater fish in a different way, it is conceivable that pharmacokinetic (PK) behavior should also exhibit salinity-dependency. The current study aimed to investigate the effect of salinity on PK of florfenicol (FF) in Nile tilapia reared at 0, 2, 4, 8, and 15 ppt after a single intravenous (IV) or oral (PO) administration of 15 mg/kg at 28 degrees C. The implication of salinity-dependent PK in the optimal dosing regimen determination was also examined. The serum concentrations of FF were analyzed by HPLC-UV method and PK parameters were determined by the 2-compartmental model. Following IV injection, increasing water salinity from 2 to 15 ppt lead to a shorter elimination half-life (t(1/2 beta)) from 11.22 to 9.03 h, faster drug clearance (CL) from 0.047 to 0.056 L/kg/h, and smaller area under the serum concentration-time curve (AUC) from 326.19 to 267.74 h.mu g/mL, suggesting a more rapid elimination at a higher salinity level. The results from PO study were generally consistent with the IV experiment except for the unchanged AUC over a salinity range of 0 to 15 ppt likely due to greater bioavailability at higher salinity. However, the absorption rate of FF was not significantly influenced by salinity as there were no significant differences in t(1/2Ka), C-max, and T-max among the 5 salinity levels. The optimal dosing regimens were determined by the pharmacokinetic-pharmacodynamic approach for each salinity level and it was revealed that the calculated dosages were similar between 0 and 8 ppt salinity, but a higher dosage was required at 15 ppt (from 7 to 10 mg/kg/day at the MIC of 2 mu g/mL). Therefore, Nile tilapia reared at saltwater required a higher FF dosage than those cultured at freshwater.