Open AccessThe disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration
Author(s) -
Ekstrand Carl,
Nostell Katarina,
Gehring Ronette,
Bondesson Ulf,
Bröjer Johan
Publication year - 2022
Publication title -
veterinary medicine and science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.485
H-Index - 11
ISSN - 2053-1095
DOI - 10.1002/vms3.763
Subject(s) - sulfadiazine , trimethoprim , pharmacokinetics , medicine , volume of distribution , foal , pharmacology , antimicrobial , neonatal sepsis , silver sulfadiazine , antibiotics , sepsis , microbiology and biotechnology , surgery , biology , genetics , wound healing
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 ( f AUC) and the pharmacokinetic/pharmacodynamik (PK/PD)‐index f AUC/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 f AUC for trimethoprim was 11.3 μg·h/ml (7.2–15.2) and the f AUC/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 f AUC for sulfadiazine was 246.8 μg·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 μg/ml using the studied dosing regimen.