TY - JOUR
T1 - Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing
AU - Lemetayer, Julie Denise
AU - Dowling, P. M.
AU - Taylor, S. M.
AU - Papich, M. G.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg/kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high-performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0-24: minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 μg/mL, which is lower than the recommended target of 20-25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13-30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.
AB - The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg/kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high-performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0-24: minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 μg/mL, which is lower than the recommended target of 20-25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13-30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.
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U2 - 10.1111/jvp.12208
DO - 10.1111/jvp.12208
M3 - Article
C2 - 25691353
AN - SCOPUS:84940611507
VL - 38
SP - 451
EP - 456
JO - Journal of Veterinary Pharmacology and Therapeutics
JF - Journal of Veterinary Pharmacology and Therapeutics
SN - 0140-7783
IS - 5
ER -