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Pharmacokinetics and pharmacodynamics of doxycycline in a Streptococcus eq ui subsp. zooepidemicus infection model in horses
Author(s) -
Chapuis Ronan J. J.,
Smith Joe S.,
Uehlinger Fabienne D.,
Meachem Melissa,
Johnson Ron,
Dowling Patricia M.
Publication year - 2021
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12982
Subject(s) - pharmacokinetics , pharmacodynamics , horse , minimum inhibitory concentration , streptococcus equi , doxycycline , agar dilution method , plasma concentration , inoculation , pharmacology , dose , antibiotics , chemistry , medicine , microbiology and biotechnology , biology , bacteria , immunology , paleontology , genetics
The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S . zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration ( C max ) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean C max /MIC was 1.30, and mean AUC last /MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.