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

Ekstrand, Carl and Nostell, Katarina and Gehring, Ronette and Bondesson, Ulf and Bröjer, Johan (2022). The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration. Veterinary Medicine and Science. 8 :3 , 1065-1071
[Research article]

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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.

Authors/Creators:Ekstrand, Carl and Nostell, Katarina and Gehring, Ronette and Bondesson, Ulf and Bröjer, Johan
Title:The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration
Series Name/Journal:Veterinary Medicine and Science
Year of publishing :2022
Volume:8
Number:3
Page range:1065-1071
Number of Pages:7
Publisher:WILEY
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Keywords:antibiotics, horse, pharmacokinetics, potentiated sulphonamides, sepsis
URN:NBN:urn:nbn:se:slu:epsilon-p-116267
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116267
Additional ID:
Type of IDID
DOI10.1002/vms3.763
Web of Science (WoS)000754387500001
Scopus2-s2.0-85124522785
ID Code:28117
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
(VH) > Dept. of Clinical Sciences
Deposited By: SLUpub Connector
Deposited On:30 May 2022 09:00
Metadata Last Modified:30 May 2022 09:01

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