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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

Abstract

Objective

To determine pharmacokinetics of single and multiple doses of rimantadine hydrochloride in horses and to evaluate prophylactic efficacy of rimantadine in influenza virus-infected horses.

Animals

5 clinically normal horses and 8 horses seronegative to influenza A.

Procedure

Horses were given rimantadine (7 mg/kg of body weight, IV, once; 15 mg/kg, PO, once; 30 mg/kg, PO, once; and 30 mg/kg, PO, q 12 h for 4 days) to determine disposition kinetics. Efficacy in induced infections was determined in horses seronegative to influenza virus A2. Rimantadine was administered (30 mg/kg, PO, q 12 h for 7 days) beginning 12 hours before challenge-exposure to the virus.

Results

Estimated mean peak plasma concentration of rimantadine after IV administration was 2.0 µg/ml, volume of distribution (mean ± SD) at steady-state (VdSS) was 7.1 ± 1.7 L/kg, plasma clearance after IV administration was 51 ± 7 ml/min/kg, and β-phase halflife was 2.0 ± 0.4 hours. Oral administration of 15 mg of rimantadine/kg yielded peak plasma concentrations of < 50 ng/ml after 3 hours; a single oral administration of 30 mg/kg yielded mean peak plasma concentrations of 500 ng/ml with mean bioavailability (F) of 25%, β-phase half-life of 2.2 ± 0.3 hours, and clearance of 340 ± 255 ml/min/kg. Multiple doses of rimantadine provided steady-state concentrations in plasma with peak and trough concentrations (mean ± SEM) of 811 ± 97 and 161 ± 12 ng/ml, respectively. Rimantadine used prophylactically for induced influenza virus A2 infection was associated with significant decreases in rectal temperature and lung sounds.

Conclusions and Clinical Relevance

Oral administration of rimantadine to horses can safely ameliorate clinical signs of influenza virus infection. (Am J Vet Med 1999:60:888–894)

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations.

ANIMALS 8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females).

PROCEDURES Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis.

RESULTS For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs).

CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.

Full access
in American Journal of Veterinary Research