Pharmacokinetics of a Single Dose of Danofloxacin Administered Intramuscularly in Koi (Cyprinus carpio)
Abstract
Despite the frequency of antimicrobial use in companion fish there remains a paucity of pharmacokinetic studies critically evaluating commonly-employed drugs. Most pharmacokinetic studies in fish focus on compounds and species used in aquaculture; current dosing recommendations are often extrapolated from those species. Danofloxacin, a synthetic fluoroquinolone antimicrobial, is a frequently employed drug with activity against common aquatic pathogens like Flavobacterium columnare and several Aeromonas sp. Danofloxacin exhibits a low minimal inhibitory concentration against many pathogens and is often a first line treatment against infectious skin disease and septicemia in fish.1
A single 10 mg/kg dose of danofloxacin (Advocin, 180 mg/ml injectable solution, Zoetis Laboratories, Parsippany, New Jersey, USA) was administered to adult koi (Cyprinus carpio) intramuscularly into the epaxial musculature. Fish were sampled at each time point: 0.25, 0.5, 0.75, 1, 4, 12, 24, 48, 72, 96, 120, and 144 hours post-injection. Whole blood was drawn antemortem and heparinized plasma was obtained from these samples; fish were euthanized and samples of liver, spleen, gill, anterior kidney, posterior kidney, skin and muscle, and scales were collected. Plasma and tissue concentrations were determined by a validated liquid chromatography-mass spectrometry method and non-compartmental pharmacokinetic analyses were performed. Subsamples of examined tissues in a negative control group and each fish sampled at 144 hours were evaluated via histopathology.
After intramuscular administration, a peak plasma concentration of 8315.7 ng/ml was reached at 0.75 hours following injection. Residue concentrations were highest in the posterior kidney (194,635.3 ng/g), and lowest in the skin and muscle (5,726.2 ng/g) at 0.75 hours. In these fish, the plasma elimination half-life was 15 hours and drug was detected for at least 144 hours. Histopathology at 144 hours was unremarkable, there were no lesions noted in the anterior kidney, posterior kidney, liver, gills, or in the skin and muscle at the injection site. This study suggests that danofloxacin at a dose of 10 mg/kg reaches therapeutic concentrations rapidly in plasma and tissues in koi.
Acknowledgements
The authors would like to thank the technicians from the K.L. Maddy Equine Analytical Chemistry Laboratory for their assistance in analyzing study samples and the members of the Aquatic Animal Health Laboratory at University California, Davis for their husbandry care of animals involved in this study.
* Presenting author
+ Student presenter
Literature Cited
1. Lu TY, Yang YH, Xu LW, Zhao JW, Sun DJ. 2004. Acute toxicity of danofloxacin in Amur sturgeon and the body residue. J Fish Sci China. 542–548.