Doxycycline serum protein binding in pigs reveals a relatively high free fraction
Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to f...
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| Published in | Journal of veterinary pharmacology and therapeutics Vol. 46; no. 2; pp. 112 - 118 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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England
Wiley-Blackwell
01.03.2023
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| Abstract | Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to free plasma concentrations of doxycycline largely lower than the minimum inhibitory concentrations of the target pathogens. This apparent inconsistency led us to reassess plasma protein binding of doxycycline in pigs. Using an equilibrium dialysis method, the extent of doxycycline binding was measured individually in 26 pigs for total doxycycline concentration ranging from 10 to 1000 μmol/L. Analysis of the data using a non‐linear mixed‐effects model demonstrated linearity of plasma protein binding with a mean fu value of 31% and a relatively low inter‐subject variability of approximately 10%. This new data showing that the free fraction is four times greater than what could have been anticipated from historical data is discussed in particular for the calculation of the PK/PD cut‐offs, which are used to establish the clinical breakpoints for antimicrobial susceptibility testing. |
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| AbstractList | Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to free plasma concentrations of doxycycline largely lower than the minimum inhibitory concentrations of the target pathogens. This apparent inconsistency led us to reassess plasma protein binding of doxycycline in pigs. Using an equilibrium dialysis method, the extent of doxycycline binding was measured individually in 26 pigs for total doxycycline concentration ranging from 10 to 1000 μmol/L. Analysis of the data using a non-linear mixed-effects model demonstrated linearity of plasma protein binding with a mean fu value of 31% and a relatively low inter-subject variability of approximately 10%. This new data showing that the free fraction is four times greater than what could have been anticipated from historical data is discussed in particular for the calculation of the PK/PD cut-offs, which are used to establish the clinical breakpoints for antimicrobial susceptibility testing. Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to free plasma concentrations of doxycycline largely lower than the minimum inhibitory concentrations of the target pathogens. This apparent inconsistency led us to reassess plasma protein binding of doxycycline in pigs. Using an equilibrium dialysis method, the extent of doxycycline binding was measured individually in 26 pigs for total doxycycline concentration ranging from 10 to 1000 μmol/L. Analysis of the data using a non-linear mixed-effects model demonstrated linearity of plasma protein binding with a mean fu value of 31% and a relatively low inter-subject variability of approximately 10%. This new data showing that the free fraction is four times greater than what could have been anticipated from historical data is discussed in particular for the calculation of the PK/PD cut-offs, which are used to establish the clinical breakpoints for antimicrobial susceptibility testing.Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to free plasma concentrations of doxycycline largely lower than the minimum inhibitory concentrations of the target pathogens. This apparent inconsistency led us to reassess plasma protein binding of doxycycline in pigs. Using an equilibrium dialysis method, the extent of doxycycline binding was measured individually in 26 pigs for total doxycycline concentration ranging from 10 to 1000 μmol/L. Analysis of the data using a non-linear mixed-effects model demonstrated linearity of plasma protein binding with a mean fu value of 31% and a relatively low inter-subject variability of approximately 10%. This new data showing that the free fraction is four times greater than what could have been anticipated from historical data is discussed in particular for the calculation of the PK/PD cut-offs, which are used to establish the clinical breakpoints for antimicrobial susceptibility testing. Doxycycline is an antibiotic widely used in pig farming. As with all antibiotics, only the free concentrations are considered to be bacteriologically active. Historically, the free fraction (fu) in pig plasma has been estimated at 7%, which, given the effective dosage regime used in pigs, leads to free plasma concentrations of doxycycline largely lower than the minimum inhibitory concentrations of the target pathogens. This apparent inconsistency led us to reassess plasma protein binding of doxycycline in pigs. Using an equilibrium dialysis method, the extent of doxycycline binding was measured individually in 26 pigs for total doxycycline concentration ranging from 10 to 1000 mu mol/L. Analysis of the data using a non-linear mixed-effects model demonstrated linearity of plasma protein binding with a mean fu value of 31% and a relatively low inter-subject variability of approximately 10%. This new data showing that the free fraction is four times greater than what could have been anticipated from historical data is discussed in particular for the calculation of the PK/PD cut-offs, which are used to establish the clinical breakpoints for antimicrobial susceptibility testing. |
| Author | Bousquet‐Mélou, Alain Roques, Béatrice B. Lacroix, Marlène Z. Toutain, Pierre‐Louis Portugal, Felipe Ramon Gayrard, Véronique |
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| Cites_doi | 10.1002/jps.23872 10.1128/microbiolspec.ARBA‐0001‐2017 10.1128/AAC.00240‐16 10.1111/jvp.12512 10.1136/vr.143.10.269 10.1111/j.1365‐2885.1989.tb00670.x 10.1046/j.1365-2885.2000.00235.x 10.1046/j.1365-2885.2002.00442.x 10.1016/S0034‐5288(02)00039‐5 10.1016/j.rvsc.2018.09.004 10.1016/j.ijantimicag.2016.12.008 10.1023/a:1011507100493 10.1038/sj.clpt.6100241 10.3389/fmicb.2017.02344 10.1186/s12917‐017‐1086‐4 10.1111/j.1365-2885.1989.tb00668.x 10.1016/j.vetmic.2016.04.009 10.1016/S0891-5520(20)30278-6 10.2527/jas.2005‐561 10.1093/jac/dkx039 10.1136/vr.141.2.37 10.1016/j.vas.2019.100058 10.1111/jvp.12917 10.2460/ajvr.1990.51.08.1271 10.1038/s41598‐020‐69102‐y |
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| SubjectTerms | Animals Anti-Bacterial Agents antibiotic resistance Blood Proteins dialysis Doxycycline Life Sciences pharmacology pigs PK/PD cut‐off plasma protein binding Protein Binding Swine therapeutics |
| Title | Doxycycline serum protein binding in pigs reveals a relatively high free fraction |
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