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Research article - Peer-reviewed, 2022

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

Ekstrand, Carl; Nostell, Katarina; Gehring, Ronette; Bondesson, Ulf; Brojer, Johan;

Abstract

Background: 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.Objectives: 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.Method: 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.Results: 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 mu g.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 mu g.h/ml (175.6-335.4).Conclusion: For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC-value of 0.5 mu g/ml using the studied dosing regimen.

Keywords

antibiotics; horse; pharmacokinetics; potentiated sulphonamides; sepsis

Published in

Veterinary Medicine and Science

2022, volume: 8, number: 3, pages: 1065-1071
Publisher: WILEY

Authors' information

Swedish University of Agricultural Sciences, Department of Clinical Sciences
Utrecht University
Bondesson, Ulf
National Veterinary Institute SVA
Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Clinical Science

Publication Identifiers

DOI: https://doi.org/10.1002/vms3.763

URI (permanent link to this page)

https://res.slu.se/id/publ/116267