Pharmacokinetics of enrofloxacin in fingerling rainbow trout (Oncorhynchus mykiss)

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Abstract
The pharmacokinetics of intravenously and orally administered enrofloxacin was determined in fingerling rainbow trout (Oncorhymhur mykiss). Doses of 5 or 10 mg enrofloxacin /kg body weight were administered intravenously to 26 fish for each dose and blood was sampled over a 60‐h period at 15°C. Two groups of fish were treated orally with 5, 10, or 50 mg/kg (80 fish/dose at each temperature) and held at 15°C or 10°C during the 60‐h sampling period. Following intravenous administration, the serum concentration—time data of enrofloxacin in rainbow trout were best described by a two‐compartment open model for both doses of 5 and 10 mg enrofloxacin/kg. The hybrid rate constants a and β did not differ between doses. The distributional phase was rapid with a half‐life of 6–7 min for both doses. Overall half‐lives of elimination were 24.4 h (95% CI = 20.2–30.8) and 30.4 h (24.241.0), respectively, for the 5– and 10‐mg/ kg doses. A large Vd(area) was observed following dosing of either 5 or 10 mg enrofloxacin/kg,: 3.22 and 2.56 l/kg, respectively. Whole body clearance for 5 mg/kg was 92 ml/h.kg and 58 ml/h‐kg at the 10‐mg/kg dose. Following oral administration, the serum concentration—time data for enrofloxacin were best described as a one‐compartment open model with first‐order absorption and elimination. Apparent Ka over all doses at 10°C averaged 62% less than apparent Ka, at 15°C. Estimates of the apparent t(1/2)e over both temperatures ranged from 29.5 h (18.4–73.4) to 56.3 h (38.3–106.6). Bioavailability averaged 42% over all doses at 15°C and was decreased to an average of 25% at 10°C. Peak serum concentrations appeared between 6 and 8 h following dosing. A dose of 5 mg/kg/ day was estimated to provide average steady‐state serum concentrations at 10°C that are approximately 4.5 times the highest reported MIC values for Streptococcus spp., the fish pathogen least sensitive to enrofloxacin. Owing to the long apparent half‐life of elimination of enrofloxacin in fingerling trout, it would take approximately 5 to 9 days to achieve these predicted steady‐state serum concentrations; this estimate is important when considering the duration of therapy in clinical trials.