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Doxycycline serum protein binding in pigs reveals a relatively high free fraction

Felipe Ramon, Portugal; Marlène Z., Lacroix; Béatrice B., Roques; Véronique, Gayrard; Pierre-Louis, Toutain; Bousquet-Mélou, Alain


Portugal Felipe Ramon

Lacroix Marlène Z.

Roques Béatrice B.

Gayrard Véronique

Toutain Pierre-Louis

Alain Bousquet-Mélou


Ludovic Pelligand


Doxycycline is an antibiotic widely used in pig farming, which leads to update the doses using PK/PD concepts. However, there is an impasse to estimate the PK/PD cut-off of doxycycline in pigs. Indeed, considering its 7% free fraction and the total steady state concentrations reported in pig plasma (0.35-1.5 µg/mL), the estimated free concentrations of doxycycline (0.025-0.15 µg/mL) are far lower than the tetracycline MIC50 reported for P. multocida (MIC50 = 0.5 µg/mL). This apparent discrepancy may be explained by the atypical and counter-intuitive non-linear binding of tetracyclines to serum proteins. Plasma protein binding is usually determined by pooling plasma from healthy animals, this does not take into account the inter-subject variability required to define a PK/PD cut-off.
Thus, the protein binding was determined by equilibrium dialysis using individual plasma from twenty-six pigs at doxycycline concentration ranging from 1 to 1000 µM. This study investigated both the shape and measurement of doxycycline protein binding and estimated inter-subject variability using a non-linear mixed effects model.
Our results did not indicate any “atypical” protein binding and reveals a higher free fraction of doxycycline in pig plasma than previously reported (~31%) with a relatively low between-subject variability (~10%).


Felipe Ramon, P., Marlène Z., L., Béatrice B., R., Véronique, G., Pierre-Louis, T., & Bousquet-Mélou, A. (2023). Doxycycline serum protein binding in pigs reveals a relatively high free fraction. Journal of Veterinary Pharmacology and Therapeutics,

Journal Article Type Article
Acceptance Date Dec 13, 2022
Publication Date Jan 24, 2023
Deposit Date Jan 3, 2023
Publicly Available Date Jan 25, 2024
Journal JVPT
Print ISSN 0140-7783
Publisher American Academy of Veterinary Pharmacology and Therapeutics
Peer Reviewed Peer Reviewed


Doxycycline serum protein binding in pigs reveals a relatively high free fraction. (502 Kb)


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