Effects of starvation on the pharmacokinetics and optimal dosages of florfenicol and associated serum biochemistry in Asian seabass (Lates calcarifer).

Starvation has influence on physiology and pharmacokinetic (PK) characteristics of many drugs in land animals. However, similar PK information in fish is lacking. The current study examined the effects of starvation on fish PK, taking florfenicol (FF) in Asian seabass as an example. FF was orally administered at a single dose of 10 mg/kg into 35-day starved fish reared at 25 and 30°C and the serum FF concentration was analyzed by HPLC-FLD. At 30°C, the absorption and elimination half-lives of the starved fish were increased by 30% (from 0.44 to 0.57 h) and 55% (from 7.2 to 11.18 h), respectively. The volume of distribution, clearance, and area under the curve were changed from 1.25 to 0.71 L/kg, 0.120 to 0.044 L/kg/h, and 88 to 228 h·µg/ml, respectively. Similar starvation-induced PK changes were also observed at 25°C. The serum biochemical parameters, mainly the alanine aminotransferase, aspartate aminotransferase, and glucose levels, were significantly reduced in the starvation group. Overall, FF absorption, distribution, and elimination rates were reduced by starvation, resulting in four to five times lower optimal dosage than the non-starved fish. Drug treatment in starved fish should be treated with caution as overdosing and/or tissue residues could perceivably occur.

Effects of temperature on the pharmacokinetics, optimal dosage, tissue residue, and withdrawal time of florfenicol in asian seabass (lates calcarifer).

Drug behavior in the bodies of fish is largely influenced by the water temperature. Antimicrobial drugs are needed for the control of bacterial outbreaks in farmed fish including Asian seabass (Lates calcarifer). However, little is known about the temperature effect on appropriate drug uses in this species. The purpose of this study was to investigate the differences in pharmacokinetics (PK), optimal dosages, tissue depletion, and withdrawal time (WDT) of florfenicol (FF) in Asian seabass reared at 25 and 30 °C. In the PK study, the fish were administered with a single oral dose of 10 mg/kg FF. The optimal dosing regimen was determined by the pharmacokinetic-pharmacodynamic (PK-PD) approach. In the tissue depletion and WDT study, FF was administered at the optimal dosages once daily for 5 days and the WDT was determined by linear regression analysis based on the sum of FF and its metabolite florfenicol amine (FFA) in the muscle/skin. When the temperature was increased from 25 to 30 °C, the elimination half-life of FF was significantly decreased from 11.0 to 7.2 h. While the other PK parameters were not changed significantly, the calculated optimal dosages for the target minimum inhibitory concentration (MIC) of 2 µg/mL were 10.9 and 22.0 mg/kg/day, respectively for 25 and 30 °C. The sum of FF + FFA is a preferable marker residue for WDT determination because differential FF metabolism was observed at different temperatures. The depletion half-life of the muscle/skin was shortened from 41.1 to 32.4 h by the 5 °C temperature increase. Despite different absolute amounts of FF given between the two temperature levels, the WDTs were very similar at 6-7 days. Thus, it appears that a single temperature-independent WDT can potentially be assigned when the drug was applied at the optimal dosage.