Pharmacokinetic–pharmacodynamic cutoff values for doxycycline in pigs to support the establishment of clinical breakpoints for antimicrobial susceptibility testing

Pelligand, Ludovic; Toutain, Pierre-Louis; Bouquet-Mélou, Alain; Ferran, Aude; Roques, Béatrice; del Castillo, Jérôme; Lees, Peter; Croubels, Siska; Bousquet, Eric

Abstract

This meta-analysis provides a population model of doxycycline (DOXY) disposition in pigs for computation of PK/PD cutoff values corresponding to differing modalities of DOXY administration orally in pigs. This analysis enables establishment of specific clinical breakpoints for the development of antimicrobial susceptibility testing of DOXY in pigs. The meta-analysis of 380 data sets, totaling 3295 plasma concentrations obtained from 300 pigs weighing 8.5 to 101 kg, was performed using a Non-Linear Mixed Effect Model. The plasma clearance for a typical 50 kg BW pig was estimated to be 0.259 L/kg/h with a corresponding plasma half-life of 7.33 h. The bioavailability of DOXY administered in feed under field conditions was estimated to be 50%, with a large between subject variability of 84.8%. The bioavailability of DOXY in solution in drinking water was significantly lower (30.7%) but much less variable, with a between subject variability of 34.3%. Several dosing schedules (5 to 20 mg/kg per day) for two administration modalities (drinking water vs. food) were simulated to calculate the corresponding PK/PD cutoffs. The highest PK/PD cutoff of 0.50 mg/L was obtained for DOXY administered in feed at 20 mg/kg BW.

Citation

Pelligand, L., Toutain, P.-L., Bouquet-Mélou, A., Ferran, A., Roques, B., del Castillo, J., Lees, P., Croubels, S., & Bousquet, E. (2025). Pharmacokinetic–pharmacodynamic cutoff values for doxycycline in pigs to support the establishment of clinical breakpoints for antimicrobial susceptibility testing. Journal of Veterinary Pharmacology and Therapeutics, https://doi.org/10.1111/jvp.13511

• Journal Article Type: Article
• Acceptance Date: Mar 26, 2025
• Publication Date: Apr 17, 2025
• Deposit Date: Nov 29, 2024
• Publicly Available Date: Apr 28, 2025
• Journal: JVPT
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/jvp.13511