Tissue Concentrations of Enrofloxacin, and its Metabolite Ciprofloxacin, After a Single Topical Dose in the Coqui Frog (Eleutherodactylus coqui)
Abstract
There are few studies evaluating transcutaneous absorption of antibiotics in amphibians.4-7 This study determined tissue concentrations of the fluoroquinolone antimicrobial enrofloxacin, and its active metabolite ciprofloxacin, over a 24-hour period after a single topical application in coqui frogs, Eleutherodactylus coqui. Twelve frogs, scheduled for euthanasia unrelated to the study, were randomly divided into four groups of three animals. Three groups received one dose of enrofloxacin topically (10 mg/kg), while the remaining group served as an untreated control. One group was euthanatized, and liver and kidneys were collected at 0 (control), 6, 12, and 24 hours post-treatment. Tissues were pooled per group and concentrations of enrofloxacin and ciprofloxacin were measured using high pressure liquid chromatography. Enrofloxacin tissue concentrations ranged from 0.2 to 0.44 µg/g, which is below the minimum inhibitory concentration (MIC) for susceptible organisms (0.5 µg/mL).1 Ciprofloxacin concentrations ranged from 0.42 µg/g to 0.81 µg/g, which is also below the MIC for susceptible organisms (1.0 µg/mL).1 Susceptibility levels have not been established for amphibian bacteria; therefore, MIC levels are based on plasma concentrations in domestic species.1 In vitro studies demonstrate an additive effect of enrofloxacin and ciprofloxacin concentrations for improved bacterial inhibition.3 The sum of enrofloxacin and ciprofloxacin in this study ranges from 0.78 µg/g to 1.25 µg/g, though it is not known how tissue concentrations correlate with therapeutic efficacy.1 Results of this study indicate that enrofloxacin is absorbed systemically following topical administration in coqui frogs, converts to ciprofloxacin, and measurable tissue concentrations are present for at least 24 hours.
Acknowledgments
The authors would like to thank Lisa Eidlin and the Wildlife Health Center support staff for their generous time in caring for these frogs. This study was reviewed and accepted by the Wildlife Conservation Society Institutional Animal Care and Use Committee. Project Number: 08:01
Literature Cited
1. Clinical Laboratory Standards Institute. CLSI. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Approved Standard—Third Edition. CLSI document M31-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
2. Lautzenhiser, S.J., J.P. Fialkowski, D. Bjorling, E. Rosin. 2001. In vitro antibacterial activity of enrofloxacin and ciprofloxacin in combination against Escherichia coli and staphylococcal clinical isolates from dogs. Res Vet Sci. 70:239–241.
3. McKellar, Q., I. Gibson, A. Monteiro, M. Bregante. 1999. Pharmacokinetics of enrofloxacin and danofloxacin in plasma inflammatory exudate, and bronchial secretions of calves following subcutaneous administration. Antimicrob Agents Chemother. 43:1988–1992.
4. Menard, M.R. 1984. External application of antibiotic to improve survival of adult laboratory frogs (Rana pipiens). Lab Anim Sci. 34:94–96.