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American journal of veterinary research2006; 67(6); 1076-1081; doi: 10.2460/ajvr.67.6.1076

Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses.

Abstract: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. Methods: 6 healthy mature horses. Methods: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. Results: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. Conclusions: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.
Publication Date: 2006-06-03 PubMed ID: 16740105DOI: 10.2460/ajvr.67.6.1076Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study evaluates the effect of different administration routes (intravenous, intramuscular, and intragastric) on the pharmacokinetics of difloxacin in healthy horses. The study shows that the medication may be effective for treating bacterial infections in horses.

Research Methodology

  • The researchers employed a crossover study design which included three phases, with long washout periods of 15 days between different treatments.
  • The subjects of the study comprised of six healthy mature horses. These horses were administered a 5% difloxacin formulation intravenously and intramuscularly in a single dose, whereas for the intragastric method, an oral solution was prepared and given through a nasogastric tube.
  • Blood samples were systematically collected before and at consistent intervals after each administration to monitor the concentration of difloxacin in the blood plasma.
  • A high-performance liquid chromatography assay with fluorescence detection was employed to determine these plasma difloxacin concentrations.

Findings

  • The findings suggest that the time-concentration data for difloxacin plasma following an intravenous administration can better be described by a 2-compartment open model, while a 1-compartment model was sufficient to describe the disposition of difloxacin after intramuscular or intragastric administration.
  • It was also found that the average half-life of difloxacin after being administered via intravenous, intramuscular, and intragastric routes was 2.66, 5.72, and 10.75 hours respectively.
  • The report further detailed that the clearance rate post an IV administration was 0.28 L/kg.h. The absolute mean bioavailability after intramuscular and intragastric administration was 95.81 +/- 3.11% and 68.62 +/- 10.60%, respectively.
  • A significant finding from the study was that the plasma creatine kinase activity had risen seven-fold 12 hours after intramuscular administration in comparison to the pre-injection levels, indicating possible tissue damage.

Conclusion

  • The research concluded that the findings point to the likelihood of difloxacin being effective in treating susceptible bacterial infections in horses.

Cite This Article

APA
Fernández-Varón E, Cárceles CM, Marín P, Martos N, Escudero E, Ayala I. (2006). Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses. Am J Vet Res, 67(6), 1076-1081. https://doi.org/10.2460/ajvr.67.6.1076

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 67
Issue: 6
Pages: 1076-1081

Researcher Affiliations

Fernández-Varón, Emilio
  • Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Campus de Espinardo, 30.071-Murcia, Spain.
Cárceles, Carlos M
    Marín, Pedro
      Martos, Nieves
        Escudero, Elisa
          Ayala, Ignacio

            MeSH Terms

            • Administration, Oral
            • Animals
            • Anti-Bacterial Agents / administration & dosage
            • Anti-Bacterial Agents / blood
            • Anti-Bacterial Agents / pharmacokinetics
            • Area Under Curve
            • Ciprofloxacin / administration & dosage
            • Ciprofloxacin / analogs & derivatives
            • Ciprofloxacin / blood
            • Ciprofloxacin / pharmacokinetics
            • Creatine Kinase / blood
            • Cross-Over Studies
            • Fluoroquinolones / administration & dosage
            • Fluoroquinolones / blood
            • Fluoroquinolones / pharmacokinetics
            • Half-Life
            • Horses / metabolism
            • Injections, Intramuscular
            • Injections, Intravenous

            Citations

            This article has been cited 1 times.
            1. Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM. Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development. Ther Deliv 2011 May;2(5):643-72.
              doi: 10.4155/tde.11.19pubmed: 21837267google scholar: lookup