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Pharmacokinetics, nephrotoxicosis, and in vitro antibacterial activity associated with single versus multiple (three times) daily gentamicin treatments in horses.

Abstract: Once-daily administration of aminoglycosides may be a safe and effective therapeutic regimen, on the basis of the microbiologic and pharmacokinetic characteristics of these antibiotics. This study was designed to determine serum and tissue concentrations following i.v. administration of gentamicin, at dosages of 6.6 mg/kg of body weight, every 24 hours, and 2.2 mg/kg, every 8 hours, for 10 days in adult horses. Nephrotoxicosis from these dosage regimens also was compared, and microbiologic effects, including postantibiotic effects, were determined with various concentrations of gentamicin against an equine clinical isolate of Pseudomonas aeruginosa. Treatment at the 6.6-mg/kg dosage resulted in maximal serum concentrations (77.93 +/- 19.90 micrograms/ml, mean +/- SEM) and area under the concentration-vs-time curves (83.79 +/- 14.97 micrograms.h/ml) that were significantly (P < 0.05) greater than those following treatment at the 2.2-mg/kg dosage (5.05 +/- 0.50 micrograms/ml and 6.03 +/- 0.66 micrograms.h/ml, respectively). Nephrotoxicosis was not induced with either dosage regimen, and postantibiotic effects were prolonged with a higher gentamicin concentration. This study provided evidence to support the use of once-daily gentamicin treatment in adult horses.
Publication Date: 1995-05-01 PubMed ID: 7661456
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  • Journal Article

Summary

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The research concluded that gentamicin, an antibiotic, can be administered safely to horses once daily at a dosage of 6.6mg/kg of body weight. This treatment regimen was found to be non-toxic to the kidneys and produced prolonged postantibiotic effects with higher concentration of the drug.

Objective and Methodology

  • The study aimed to determine the pharmacokinetics, nephrotoxicosis, and in vitro antibacterial activity of single versus multiple daily dosages of gentamicin on horses.
  • The scientists administered intravenous gentamicin at a dosage of 6.6mg/kg every 24 hours and 2.2mg/kg every 8 hours for 10 days on adult horses.
  • The serum and tissue concentrations of gentamicin were measured, nephrotoxicosis from the dosage regimens was compared and microbiologic effects were determined against an equine clinical isolate of Pseudomonas aeruginosa.

Findings

  • Treatment at the 6.6mg/kg dosage produced greater maximal serum concentrations and area under the concentration-vs-time curve. Essentially, this means that a single dosage of gentamicin remains present in the horse’s system for a longer duration and at a higher concentration than multiple smaller dosages.
  • No nephrotoxicosis, toxicity in the kidneys, was observed in either dosage regimen. This suggests that neither of the dosage strategies cause kidney damage in horses.
  • Postantibiotic effects were found to be prolonged with a higher concentration of gentamicin, indicating that the drug continues to have a bactericidal effect even after the drug concentration has fallen below the level that is usually considered effective.

Implication

  • The research provides evidence that implies once-daily gentamicin treatment could be employed safely in adult horses without inducing nephrotoxicosis and with an effective prolonged postantibiotic effect.

Cite This Article

APA
Godber LM, Walker RD, Stein GE, Hauptman JG, Derksen FJ. (1995). Pharmacokinetics, nephrotoxicosis, and in vitro antibacterial activity associated with single versus multiple (three times) daily gentamicin treatments in horses. Am J Vet Res, 56(5), 613-618.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 56
Issue: 5
Pages: 613-618

Researcher Affiliations

Godber, L M
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA.
Walker, R D
    Stein, G E
      Hauptman, J G
        Derksen, F J

          MeSH Terms

          • Animals
          • Dose-Response Relationship, Drug
          • Drug Administration Schedule
          • Female
          • Gentamicins / adverse effects
          • Gentamicins / pharmacokinetics
          • Gentamicins / pharmacology
          • Horses / metabolism
          • Injections, Intravenous / veterinary
          • Kidney Diseases / chemically induced
          • Kidney Diseases / veterinary
          • Male
          • Microbial Sensitivity Tests
          • Pseudomonas aeruginosa / drug effects

          Citations

          This article has been cited 3 times.
          1. Morsing MK, Larsen I, Pedersen KS, Weber NR, Nielsen JP. Efficacy of neomycin dosing regimens for treating enterotoxigenic Escherichia coli-related post-weaning diarrhoea in a Danish nursery pig herd not using medicinal zinc oxide. Porcine Health Manag 2022 Nov 4;8(1):46.
            doi: 10.1186/s40813-022-00283-wpubmed: 36333767google scholar: lookup
          2. Gestrich A, Bedenice D, Ceresia M, Zaghloul I. Pharmacokinetics of intravenous gentamicin in healthy young-adult compared to aged alpacas. J Vet Pharmacol Ther 2018 Aug;41(4):581-587.
            doi: 10.1111/jvp.12506pubmed: 29761517google scholar: lookup
          3. Bauquier JR, Boston RC, Sweeney RW, Wilkins PA, Nolen-Walston RD. Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin. J Vet Intern Med 2015 Nov-Dec;29(6):1660-6.
            doi: 10.1111/jvim.13626pubmed: 26426540google scholar: lookup