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Abstract

OBJECTIVE

To determine the pharmacokinetics of voriconazole after single IV or orally administered boluses in common ravens (Corvus corax).

ANIMALS

8 healthy common ravens.

PROCEDURES

Voriconazole (5 mg/mL, 10 mg/kg IV) was administered to 8 birds, and then plasma voriconazole concentrations were measured at various time points by high-pressure liquid chromatography with mass spectrometry. Starting 6 months later in a randomized 3-treatment 3-period regimen, birds received a single oral dose of voriconazole suspension (10 mg/mL; 6, 12, and 24 mg/kg PO). The study period was May 2015 to March 2016.

RESULTS

Voriconazole (10 mg/kg IV) achieved an initial plasma concentration of 6.31 µg/mL when measured over 21 hours. After oral administration of voriconazole at 6, 12, and 24 mg/kg, the relative bioavailability was 67.5%, 209%, and 183%, respectively. For the 6-mg/kg dose, the maximum plasma concentration was reached at 30 minutes after administration and remained in the therapeutic range of 0.5 to 1 µg/mL for approximately 15 hours. The 12- and 24-mg/kg doses resulted in concentrations in a potentially toxic range.

CLINICAL RELEVANCE

Voriconazole was well tolerated. All 4 doses resulted in plasma concentrations of voriconazole > 0.5 µg/mL, which is the minimum inhibitory concentration recommended for pathogenic species of Aspergillus fungi known to affect birds. A single dose of voriconazole administered as 10 mg/kg IV or 6 mg/kg PO resulted in recommended target plasma concentrations. Administration of voriconazole 6 mg/kg PO 2 to 3 times daily may be adequate for treatment without exceeding the toxic range.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine if a cytochrome (CYP) P450 enzyme inhibitor can maintain therapeutic plasma levels of voriconazole when administered orally.

ANIMALS

11 healthy, common ravens (Corvus corax).

METHODS

Birds were randomly assigned to pilot study groups to receive voriconazole orally alone or combined with a CYP inhibitor. Pilot studies with 3 CYP inhibitors launched the main study using ciprofloxacin (20 mg/kg) followed 1 hour later by voriconazole (6 mg/kg) every 12 hours for 14 days. Plasma voriconazole concentrations were measured at various time points by HPLC-MS. The study period lasted from September 2016 to December 2020.

RESULTS

The birds failed to maintain therapeutic plasma levels of voriconazole during multidose administration alone or following preadministration with various CYP inhibitors. For the 14-day study period, voriconazole reached a maximum plasma concentration of 2.99 μg/mL with a time-to-peak drug concentration of 1.2 hours following preadministration of ciprofloxacin. One bird was removed from the study due to lethargy, but the other birds completed the study without incident.

CLINICAL RELEVANCE

Ciprofloxacin (20 mg/kg) followed by voriconazole (6 mg/kg) maintained the concentration of voriconazole within the recommended therapeutic range of 0.5 to 5 μg/mL without toxicity. Ciprofloxacin prevented the saturable metabolism of voriconazole and maintained these levels for the study duration. This drug combination could be used in the treatment of chronic aspergillosis in the common raven.

Open access
in American Journal of Veterinary Research