Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses

Carmen M. H. Colitz Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210

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Federico G. Latimer Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210

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Hao Cheng Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210

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Ken K. Chan Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210

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Stephen M. Reed Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210

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Genneth J. Pennick Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229-3900.

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Abstract

Objective—To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses.

Animals—6 clinically normal adult horses.

Procedures—All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed.

Results—Mean ± SD volume of distribution at steady state was 1,604.9 ± 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 ± 19%; the highest plasma concentration of 6.1 ± 1.4 μg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 μg/mL, and mean trough plasma concentration was 1.32 μg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 ± 1.594 μg/mL, 2.508 ± 1.616 μg/mL, 3.073 ± 2.093 μg/mL, 4.422 ± 0.8095 μg/mL, and 3.376 ± 1.297 μg/mL, respectively.

Conclusions and Clinical Relevance—Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.

Abstract

Objective—To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses.

Animals—6 clinically normal adult horses.

Procedures—All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed.

Results—Mean ± SD volume of distribution at steady state was 1,604.9 ± 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 ± 19%; the highest plasma concentration of 6.1 ± 1.4 μg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 μg/mL, and mean trough plasma concentration was 1.32 μg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 ± 1.594 μg/mL, 2.508 ± 1.616 μg/mL, 3.073 ± 2.093 μg/mL, 4.422 ± 0.8095 μg/mL, and 3.376 ± 1.297 μg/mL, respectively.

Conclusions and Clinical Relevance—Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.

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