Pharmacokinetics of enrofloxacin in fingerling rainbow trout (Oncorhynchus mykiss).
The pharmacokinetics of intravenously and orally administered enrofloxacin was determined in fingerling rainbow trout (Oncorhynchus 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 degrees 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 degrees C or 10 degrees 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 alpha and beta 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 (24.2-41.0), 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 degrees C averaged 62% less than apparent Ka at 15 degrees 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 degrees C and was decreased to an average of 25% at 10 degrees 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 degrees 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.
Bowser
P R
PR
Department of Avian and Aquatic Animal Medicine, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Wooster
G A
GA
St Leger
J
J
Babish
J G
JG
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D000077422:Enrofloxacin; D024841:Fluoroquinolones; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012474:Salmon / Q000378:metabolism*; D013696:Temperature; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin