Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing

Abstract

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.

Voriconazole Concentrations in Cerebrospinal Fluid During Prophylactic Use in Children with Acute Myelogenous Leukemia

“…2 There have been only a few reports describing the transfer of VRCZ to cerebrospinal fluid (CSF). [3][4][5] Here, we report analysis of VRCZ concentrations in CSF during prophylactic use in pediatric patients with acute myelogenous leukemia (AML).…”

Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic‐pharmacodynamic analysis of tear fluid following oral administration

“…Previous studies have similarly reported rapid increases in plasma concentrations of this drug after oral administration in horses, human beings, dogs, and cats. 20,33,35,36 This has been attributed to the high solubility and permeability of voriconazole. 33 It was confirmed that voriconazole was absorbed rapidly in healthy horses after a single oral administration in this study.…”

Comparison of the pharmacokinetic profiles of two different amphotericin B formulations in healthy dogs

“…(iv) Despite its long history of usage, much is still unknown concerning the pharmacokinetics of amphotericin B, especially in the veterinary treatment (Davis, Papich, & Heit, 2009). Moreover, data on the pharmacokinetics of amphotericin B‐containing liposomes are scarce in the literature and are mostly obtained from beagle dogs (Fukui et al., ; Serrano et al., ), which have generally different pharmacokinetics from the other breeds (Lemetayer, Dowling, Taylor, & Papich, ). The present study was therefore conducted with mixed breed dogs instead of beagle dogs, to represent the pharmacokinetics of general dog population more precisely.…”