Article Dans Une Revue Veterinary Quarterly Année : 2025

Population pharmacokinetic modeling of sulfadimethoxine, sulfadiazine and sulfamethoxazole combined to trimethoprim in pigs

Résumé

Sulfonamides (S) are old antibiotics combined with trimethoprim (TMP) for synergistic effects against pathogens responsible for a variety of infections in food-producing animals. In growing pigs, the TMP:S ratio is 1:5 based on human TMP/sulfamethoxazole (SMX) dosing which aims to obtain an in vivo ratio concentration of 1:19 considered as optimal against human pathogens. However, different sulfonamides with different pharmacokinetic profiles are used in pigs limiting this direct extrapolation from human. The aim was to conduct a PK study in pigs for three commonly used TMP/S combinations and to analyze data using population pharmacokinetic modeling. We found that a 2-compartment structural model fitted best the four drug PK data. TMP has the highest clearance values (0.48 L/h/kg) compared to SMX (0.21 L/h/kg), SDZ (0.12 L/h/kg) and SDMX (0.015 L/h/kg). SDMX has the longest plasma elimination half-life (14.8 h), followed by SDZ (3.7 h), TMP (2.9 h) and SMX (2.2 h). Monte Carlo simulations (n = 50,000 pigs) showed that only for 8.8%, 46.8%, and 76.5% of pigs for TMP/SMX, TMP/SDZ and TMP/SDMX, respectively, the free plasma concentration ratio fell within the range of 1:10–1:50 at the marketed doses administered. These results should be further linked to pharmacodynamics to optimize the use of these important antimicrobials drugs in veterinary medicine.

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hal-05290011 , version 1 (30-09-2025)

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Marine Boulanger, Jean-François Taillandier, Jérôme Henri, Mathias Devreese, Siegrid de Baere, et al.. Population pharmacokinetic modeling of sulfadimethoxine, sulfadiazine and sulfamethoxazole combined to trimethoprim in pigs. Veterinary Quarterly, 2025, 45 (1), pp.2565351. ⟨10.1080/01652176.2025.2565351⟩. ⟨hal-05290011⟩
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