Pharmacokinetics of a single dose of voriconazole administered orally with and without food to red-tailed hawks (Buteo jamaicensus)

Abstract

OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.

Single oral or intravenous administration of voriconazole achieved recommended therapeutic minimum inhibitory concentrations against Aspergillus in the common raven (Corvus corax)

“…The measured t max ranged from 2 to 4.5 hours, indicating rapid gastric emptying. This was 1 to 2 times that observed in humans, 8 and similar to the findings in hawks, 1,33 horses, 4,5 cats, 7 parrots, 10,11 ducks, 16 dogs, and most rodent species. 8 The relative bioavailability was 67.5% for the 6-mg/kg PO dose, and this exceeded the values observed for most avian species studied to date.…”

“…17 Food has been shown to reduce the oral bioavailability in humans by 22%, and the absorption time in humans 27,36 and hawks. 1 Red-tailed hawks in another study 33 had a relative bioavailability of 97% when voriconazole was given through a gavage tube separately, followed by gavage of a liquid diet. Birds were fed 1 hour after treatment.…”

“…9 To our knowledge, voriconazole has only been studied in 9 genera and 16 species of birds, include the Timneh parrot (Psittacus timneh), 10 Hispaniolan Amazon parrot (Amazona ventralis), 11 Japanese quail (Coturnix japonica), 12 domestic chicken (Gallus gallus domesticus), 13 pigeon (Columba livia domestica), 14 6 penguin species, 15 mallard duck (Anas platyrhynchos), 16 3 falcon species, 17,18 and the red-tailed hawk (Buteo jamaicensus). 1 The PK of voriconazole show marked variability among the species tested. Currently, voriconazole is the treatment of choice against systemic aspergillosis in humans because of to its wide tissue distribution, safety, and tolerance.…”

Clinical Management of Avian Renal Disease

“…Data from Refs. 57,69,71,72,75,[78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95] Succimer (meso 2,3-dimercaptosuccinic acid or DMA) is an oral chelator, derived from British Anti-Lewisite capable of chelating lead from soft tissues, but not from bone. 107 Succimer is less efficient in cases of zinc intoxication.…”

Application of different pharmacokinetic models to describe and predict pharmacokinetics of voriconazole in magellanic penguins following oral administration

“…The pharmacokinetics of voriconazole have been reasonably well‐studied in different bird species including red‐tailed hawks (Gentry et al., ; Parsley, Tell, & Gehring, ), several species of parrots (Flammer et al., ; Sanchez‐Migallon Guzman et al., ), chickens (Burhenne, Haefeli, Hess, & Scope, ), and Japanese quail (Souza, Redig, & Cox, ; Tell et al., ). To date, only one study assessed voriconazole pharmacokinetics in penguins (Hyatt, Wiederhold, Hope, & Stott, ).…”