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Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid.
Abstract: The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half-life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax ) of N-desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.
© 2014 John Wiley & Sons Ltd.
Publication Date: 2014-09-16 PubMed ID: 25224604DOI: 10.1111/jvp.12152Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
- Adult Horses
- Antibiotics
- Bioavailability
- Clinical Study
- Drug
- Equine Health
- Intramuscular Administration
- Intravenous Administration
- Mass Spectrometry
- Metabolites
- Minimum Inhibitory Concentration
- Oral Administration
- Pharmacodynamics
- Pharmacokinetics
- Physiology
- Simulation
- Synovial Fluid
- Veterinary Medicine
- Veterinary Procedure
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research reveals how the antibiotic drug, danofloxacin, and its metabolite, N-desmethyldanofloxacin, behave within adult horses when administered via different methods. It suggests that the drug’s effectiveness can vary significantly depending on whether it is introduced intravenously, intramuscularly, or intragastrically.
Objectives and Structure of the Study
- The study aimed to understand the behaviour (or pharmacokinetics) of danofloxacin, and its metabolite, N-desmethyldanofloxacin when administered to adult horses.
- Part of the objective was also to assess the concentration of these substances in the synovial fluid of horses (a type of fluid found in the cavities of synovial joints).
- The study involved administering danofloxacin to six adult mares through different methods – intravenously, intramuscularly and intragastrically. The doses varied according to each administration method.
Methodology and Results of the Study
- The concentrations of the drug and metabolite were measured using a process called Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS).
- Through this measurement process, the study found that maximum plasma concentration of N-desmethyldanofloxacin was achieved within 5 minutes of intravenous administration.
- It was also revealed that the peak levels of danofloxacin were significantly higher when administered intramuscularly compared to intragastrically.
- Furthermore, the bioavailability of the drug was found to be much higher when administered intramuscularly compared to intragastrically.
- In terms of synovial fluid concentration, the levels were significantly higher when the drug was administered intravenously and intramuscularly compared to intragastrically.
- Simulations suggested that danofloxacin would be most effective against bacteria with a minimum inhibitory concentration (MIC) of 0.25 μg/mL when administered intravenously or intramuscularly, and 0.12 μg/mL when administered orally, to maintain an area under the curve:MIC ratio that is equal to or above 50.
Conclusion
- Overall, the study provided valuable insights into how administration methods can significantly impact danofloxacin’s behaviour and effectiveness within the horses’ bodies.
- These findings could influence the choice of drug administration routes for horses in the future.
Cite This Article
APA
Lopez BS, Giguère S, Berghaus LJ, Mullins MA, Davis JL.
(2014).
Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid.
J Vet Pharmacol Ther, 38(2), 123-129.
https://doi.org/10.1111/jvp.12152 Publication
Researcher Affiliations
- Department of Large Animal Medicine, University of Georgia, Athens, GA, USA.
MeSH Terms
- Animals
- Area Under Curve
- Biological Availability
- Female
- Fluoroquinolones / blood
- Fluoroquinolones / chemistry
- Fluoroquinolones / metabolism
- Fluoroquinolones / pharmacokinetics
- Half-Life
- Horses / blood
- Injections, Intramuscular
- Injections, Intravenous
- Quinolones / blood
- Quinolones / chemistry
- Quinolones / metabolism
- Quinolones / pharmacokinetics
- Synovial Fluid / chemistry
Citations
This article has been cited 2 times.- Totten KMC, Cunningham SA, Gades NM, Etzioni A, Patel R. Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits. Front Pharmacol 2022;13:840165.
- Corum O, Corum DD, Altan F, Er A, Cetin G, Uney K. Pharmacokinetics of intravenous and intramuscular danofloxacin in red-eared slider turtles (Trachemys scripta elegans). J Vet Med Sci 2019 May 31;81(5):753-757.
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