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

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  • 1 Department of Companion Animal and Special Species, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Present address: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 3 Department of Companion Animal and Special Species, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 4 Department of Companion Animal and Special Species, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 5 Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

Objective—To determine the pharmacokinetics of fluconazole in horses.

Animals—6 clinically normal adult horses.

Procedure—Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose.

Results—Mean (± SD) apparent volume of distribution of fluconazole at steady state was 1.21 ± 0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively. Maximum plasma concentrations and terminal halflives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50 ± 23.88, 14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ± 32.87 µg/ml, respectively.

Conclusion and Clinical Relevance—Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses. (Am J Vet Res 2001;62:1606–1611).

Abstract

Objective—To determine the pharmacokinetics of fluconazole in horses.

Animals—6 clinically normal adult horses.

Procedure—Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose.

Results—Mean (± SD) apparent volume of distribution of fluconazole at steady state was 1.21 ± 0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively. Maximum plasma concentrations and terminal halflives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50 ± 23.88, 14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ± 32.87 µg/ml, respectively.

Conclusion and Clinical Relevance—Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses. (Am J Vet Res 2001;62:1606–1611).