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Single and multiple dose pharmacokinetics of gentamicin administered intravenously and intramuscularly in adult conditioned thoroughbred mares.

Abstract: The pharmacokinetics of gentamicin following single and multiple intravenous and intramuscular doses were compared in a two phase, randomised cross-over study in horses. Gentamicin was administered to 6 healthy, conditioned Thoroughbred mares at a dosage of 3.3 mg/kg body weight every 12 hours for 5 intravenous or intramuscular consecutive treatments. Equal numbers of horses were treated by either route during each phase. There was a wash-out period of 5 days between phases. During each phase serial blood samples were collected from each mare immediately before treatment and at 16 intervals following the first and fifth administrations. Blood samples were also collected immediately before treatment and at 30 and 60 minutes following doses 2 through to 4. Gentamicin plasma concentrations were determined by fluorescence polarisation immunoassay. Plasma gentamicin concentration versus time data for both single and multiple doses by either route was best described by a 2 compartmental open model with first order rate constants. A distribution half-life (T1/2 alpha) of 0.1 +/- 0.1 hours, terminal half-life (T1/2 beta) of 1.2 +/- 0.2 hours, mean residence time (MRT) of 1.4 +/- 0.1 hours and total body clearance (ClB) of 1.4 +/- 0.2 ml/kg/min were observed following multidose gentamicin intravenous administration. The volume of distribution at steady state (Vdss) was 117.6 +/- 10.8 ml/kg. No significant differences (P > 0.05) were observed for any of the parameters between single or multiple doses for either route of administration. Except for AUC, significant (P < or = 0.05) differences were observed between multiple intravenous and intramuscular treatments for all pharmacokinetic parameters determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1995-09-01 PubMed ID: 8596186
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  • Clinical Trial
  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

Summary

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The research investigated how the drug gentamicin is absorbed and processed in the body of adult Thoroughbred mares. The study found that the rate of absorption and processing was consistent regardless of whether the drug was given intravenously or intramuscularly, and whether it was administered once or multiple times.

About the Study

  • In this experiment, the researchers looked at the pharmacokinetics (how drugs are absorbed, distributed, metabolized, and excreted by the body) of the antibiotic gentamicin in 6 adult Thoroughbred mares. This was done in a two-phase, randomized cross-over study, where the horses were administered the drug either intravenously (directly into their blood) or intramuscularly (into their muscles).
  • The doses were given at a ratio of 3.3 mg per kg of body weight every 12 hours, for five consecutive treatments. Equal numbers of mares were subjected to each method of administration in each phase.
  • Between the two phases, a wash-out period of 5 days was observed to ensure the drug was completely removed from the horses’ bodies before starting the next phase. Multiple blood samples were taken from each mare during the process to monitor how the drug was processed in their bodies.

Results and Findings

  • The results showed that plasma gentamicin concentration versus time data for both single and multiple doses given via either route was best described by a two-compartmental open model with first order rate constants. Essentially, this means that gentamicin was distributed and eliminated from the body in two phases.
  • The first phase (distribution phase), which happens rapidly, had a half-life of 0.1 +/- 0.1 hours. The second (elimination phase), which is slower, had a half-life of 1.2 +/- 0.2 hours. The mean residence time (the average time the drug stays in the body) was 1.4 +/- 0.1 hours, and the total clearance rate was 1.4 +/- 0.2 ml/kg/min.
  • No significant differences were observed for any of these parameters between single or multiple doses or different routes of administration. However, there were significant differences between multiple intravenous and intramuscular treatments for all the pharmacokinetic parameters determined, except for the Area Under the Curve (AUC) – a measure of total drug exposure over time.

Cite This Article

APA
Swan GE, Guthrie AJ, Mülders MS, Killeen VM, Nurton JP, Short CR, van den Berg JS. (1995). Single and multiple dose pharmacokinetics of gentamicin administered intravenously and intramuscularly in adult conditioned thoroughbred mares. J S Afr Vet Assoc, 66(3), 151-156.

Publication

ISSN: 1019-9128
NlmUniqueID: 7503122
Country: South Africa
Language: English
Volume: 66
Issue: 3
Pages: 151-156

Researcher Affiliations

Swan, G E
  • Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Republic of South Africa.
Guthrie, A J
    Mülders, M S
      Killeen, V M
        Nurton, J P
          Short, C R
            van den Berg, J S

              MeSH Terms

              • Animals
              • Anti-Bacterial Agents / administration & dosage
              • Anti-Bacterial Agents / blood
              • Anti-Bacterial Agents / pharmacokinetics
              • Cross-Over Studies
              • Female
              • Fluorescence Polarization Immunoassay
              • Gentamicins / administration & dosage
              • Gentamicins / blood
              • Gentamicins / pharmacokinetics
              • Horses / blood
              • Injections, Intramuscular
              • Injections, Intravenous

              Citations

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