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Home / Equine Research Bank / Vet Med Sci / The disposition of trimethoprim and sulfadiazine in neonatal...
Veterinary medicine and science2022; 8(3); 1065-1071; doi: 10.1002/vms3.763

The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration.

Abstract: Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life-threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentration (MIC) for Escherichia coli, a recognized pathogen in neonatal foal sepsis. A total of five doses of trimethoprim (2.5 mg/kg) and sulfadiazine (12.5 mg/kg) were administered intravenously every 12 h to eight neonatal foals that were 3 days old at inclusion. A non-linear mixed effects model was fitted to the trimethoprim and sulfadiazine experimental data. The 24 h area under the free plasma trimethoprim and sulfadiazine concentration-time curves (fAUC) and the pharmacokinetic/pharmacodynamik (PK/PD)-index fAUC/MIC was calculated to evaluate the potential clinical benefits of the administered dose. For trimethoprim, the typical values were 1.99 L/kg, 0.33 L/h·kg and 4.2 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for trimethoprim was 11.3 μg·h/ml (7.2-15.2) and the fAUC/MIC ratio for E. coli was 23 (16.4-29.2) (population mean (range)). For sulfadiazine, the typical values were 0.61 L/kg, 0.09 L/h·kg and 5.3 h for the apparent volume of distribution, clearance and terminal half-life, respectively. The 24 h fAUC for sulfadiazine was 246.8 μg·h/ml (175.6-335.4). For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC-value of 0.5 μg/ml using the studied dosing regimen.
© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.
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Publication Date: 2022-02-13 PubMed ID: 35152563PubMed Central: PMC9122441DOI: 10.1002/vms3.763Google Scholar: Lookup
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Summary

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The research article explores how the antimicrobial drugs trimethoprim and sulfadiazine interact within the bodies of neonatal foals. The study highlights that for some foals, the current dosage may not be enough to successfully treat bacterial infections.

Research Context

  • Septicaemia is a potentially fatal condition in neonatal foals caused by Gram positive and Gram negative bacteria. This condition requires the immediate commencement of broad-spectrum antimicrobial drugs.
  • Potentiated sulphonamides, such as trimethoprim combined with sulfadiazine, are considered potential treatment options. However, prior to this study, their pharmacokinetics, or how the drugs move within the body of neonatal foals, were unknown.
  • Understanding the effective dosage and movement of these drugs is critical to assess their effectiveness against pathogens like E. coli, which is associated with neonatal foal sepsis.

Research Methodology

  • A total of five doses of trimethoprim and sulfadiazine were administered every 12 hours to eight neonatal foals that were 3 days old at inclusion.
  • A non-linear mixed effects model was applied to the trimethoprim and sulfadiazine experimental data. This mathematical model is commonly used in pharmacokinetics to estimate pharmacological parameters.
  • The area under the ‘free plasma concentration-time’ curve and the pharmacokinetic/pharmacodynamic index were calculated. These assess the volume and distribution, clearance, and terminal half-life of the drugs, giving an insight into drug exposure over time.

Research Findings

  • The research revealed that for trimethoprim, the typical values were 1.99 L/kg for the apparent volume of distribution, 0.33 L/h·kg for clearance and 4.2 hours for terminal half-life.
  • For sulfadiazine, the typical values were 0.61 L/kg for the apparent volume of distribution, 0.09 L/h·kg for clearance and 5.3 hours for the terminal half-life.
  • The fAUC/MIC ratio for E. coli was 23 for trimethoprim, which indicates its strength against the bacterium.
  • However, the study found that the plasma exposure of trimethoprim is insufficient in some foals to successfully treat bacterial infections with a minimum inhibitory concentration (MIC) value of 0.5 μg/ml using the studied dosing regimen.

Implications of the Study

  • This study gives important insights into the pharmacokinetics of trimethoprim and sulfadiazine in neonatal foals, providing evidence for potential adjustments to treatment strategies for foal sepsis.
  • The findings suggest that there may be a need to administer higher doses of trimethoprim for successful treatment of bacterial infections in some foals.

Cite This Article

APA
Ekstrand C, Nostell K, Gehring R, Bondesson U, Bröjer J. (2022). The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration. Vet Med Sci, 8(3), 1065-1071. https://doi.org/10.1002/vms3.763

Publication

Veterinary medicine and science
ISSN: 2053-1095
NlmUniqueID: 101678837
Country: England
Language: English
Volume: 8
Issue: 3
Pages: 1065-1071

Researcher Affiliations

Ekstrand, Carl
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Nostell, Katarina
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Gehring, Ronette
  • Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Department of Population Health Sciences, Division of Veterinary and Comparative Pharmacology, Utrecht University, Utrecht, The Netherlands.
Bondesson, Ulf
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.
Bröjer, Johan
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Administration, Intravenous / veterinary
  • Animals
  • Anti-Bacterial Agents
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / therapeutic use
  • Escherichia coli
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Horses
  • Sulfadiazine / pharmacokinetics
  • Trimethoprim / therapeutic use

Conflict of Interest Statement

The authors declare no conflict of interest.

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