Multiple route and dose pharmacokinetics of enrofloxacin in juvenile Atlantic salmon

Abstract

The fluoroquinolone antibacterial family is a relatively recent group of bactericidal compounds, generally characterized by efficacy against a wide spectrum of bacterial organisms and exhibiting minimal adverse effects in treated patients. The fluoroquinolones are widely prescribed in both human and veterinary medicine, though in veterinary medicine in the USA there are currently only two approved compounds, enrofloxacin (Baytril, Bayer Animal Health, Shawnee Mission, KS) and sarafloxacin (SaraFlox, Abbott Laboratories, North Chicago, IL), both with limited species and disease label approvals. Currently, there are no approved fluoroquinolone antibacterials to treat bacterial infectious diseases in cultured fish species. Enrofloxacin was administered to juvenile Atlantic salmon as a single bolus via intraarterial (i.a.), intraperitoneal (i.p.), intramuscular (i.m.), or oral gavage routes of administration. The drug was administered via the first three routes to achieve a dose of 10 mg/kg, and via oral gavage to achieve both 10 (p.o.-10) and 5 (p.o.-5) mg/kg doses. Two-compartment model kinetics were observed with elimination of half-lives (t1/2) of 130.6, 34.32, 84.98, 105.11, and 48.24 h, area under the drug concentration-time curves (AUC) of 84.3, 75.31, 55.61, 41.68, and 38.81 micrograms x h/mL, and bioavailabilities (F) of 100, 89.34, 65.97, 49.44, and 46.04% (i.a., i.p., i.m., p.o.-10, p.o.-5, respectively). All administration routes at 10 mg/kg were found to yield comparable drug concentration-time curves for multiple tissue, indicating no distinct advantage of using one route over another from a kinetics perspective. Finally, the 5 mg/kg dose (p.o.-5) yielded comparable multiple tissue drug concentration-time curves to the 10 mg/kg dose (p.o.-10), providing pharmacokinetic evidence to justify therapeutic efficacy trials with the lower dose.

Pharmacokinetics and tissue behavior of enrofloxacin and its metabolite ciprofloxacin in turbot Scophthalmus maximus at two water temperatures

“…in Scophthalmus maximus ( n =5), at 16°C and 10°C water temperatures the present study at 10°C was higher than the previous report of 25% in fi ngerling rainbow trout dosed at 10 mg enrofl oxacin/kg in freshwater at 10°C (Bowser et al, 1992). The bioavailability in this study was lower than the 55% of Atlantic salmon dosed at 10 mg/kg in seawater at 10°C (Martinsen et al, 1995), but was similar to 49.44% and 46.04% of juvenile Atlantic salmon after oral administration at 10 mg/kg and 5 mg/kg, respectively, at 9.7°C (Stoffregen et al, 1997). At 16°C, the bioavailability of enrofl oxacin was 66.13% in this study, which was higher than the 50.82% at 10°C and the profi les studied previously.…”

Long Depletion Time of Enrofloxacin in Rainbow Trout ( Oncorhynchus mykiss )

“…Studies on the pharmacokinetics of enrofloxacin in a variety of fish species, mainly salmonids, treated by the oral or the parenteral route at doses ranging from 5 to 50 mg kg Ϫ1 have been published (4,25,26,29,33). In contrast, very few studies on the pharmacokinetics of the quinolones in fishes treated with multiple doses of medicated feed and reared under field conditions have been carried out (27,32,35).…”

“…1b). Some microbiological, metabolism and pharmacokinetic aspects of enrofloxacin have been reported from previous studies with fishes (3,4,11,25,26,29,33); however, very few data on enrofloxacin depletion in fishes reared under field conditions are available (11,32).…”

Rule of accumulation of enrofloxacin in Acipenser baerii and drug-induced damage to the tissues

“…12 Juvenile Salmo salar fed with 10 mg/kg and 5 mg/kg ENX by gavage did not show significant differences in drug accumulation in different tissues. 13 However, the biological utilization rate of 53% in Oncorhynchus mykiss after oral gavage of 5 mg/kg ENX at 15 C was far higher than that (9%) in O. mykiss after oral gavage of 50 mg/kg ENX at 10 C. 14 Intraperitoneal injection of ENX usually resulted in a fast absorption, shorter time ....................................................................................................................... interval to peak concentration and a higher concentration compared with oral gavage. 15 The safe dose of ENX for sturgeons (159 mg/kg) 16 is similar to that for Cyprinus carpio var.…”