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devoid of organisms, detection of Histoplasma antigen in urine by enzyme immunoassay has been shown to be highly sensitive (94%) and specific (97% to 100%) in diagnosing feline histoplasmosis cases. 6 , 13 Itraconazole and fluconazole, sometimes in

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in Journal of the American Veterinary Medical Association

safety. Additional pharmacokinetic information is needed to guide the treatment of fungal diseases in psittacines. Fluconazole is a synthetic bis-triazole antifungal agent that is available in preparations for IV or oral administration. It is now

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in American Journal of Veterinary Research

and FDA-approved products in veterinary medicine. 8–13 Fluconazole is available as FDA-approved products (pioneer and generic) and as compounded products. Used in veterinary medicine for the treatment of numerous cutaneous and noncutaneous fungal

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in American Journal of Veterinary Research

for ≥ 8 hours after methadone was administered orally with fluconazole as a pharmacokinetic enhancer, compared with oral methadone administration alone in dogs. 9 Rectal temperature decreases are predictable in dogs after opioid administration and are

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in American Journal of Veterinary Research

referable to the organs that are affected. Common sites of infection and dissemination include the lungs, tracheobronchial lymph nodes, bones, CNS, heart, and eyes. Treatment usually includes long-term administration of an azole antifungal. 1 Fluconazole is

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in Journal of the American Veterinary Medical Association

, methadone has a relatively short half-life due to rapid hepatic metabolism presumably by the enzyme cytochrome P450. 1 , 3 , 7 , 8 Fluconazole acts as a pharmacokinetic enhancer of orally administered methadone in dogs by inhibiting this rapid metabolism

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in American Journal of Veterinary Research

anesthetized for ocular surgery that have been administered fluconazole for treatment of fungal keratitis have longer recovery times from general anesthesia (induced with ketamine and midazolam) and greater muscle weakness, ataxia, and incoordination than

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in Journal of the American Veterinary Medical Association

chloramphenicol could limit its widespread use. 4,8 Additional studies have documented that fluconazole is a pharmacokinetic enhancer of methadone in dogs. 5 In contrast to chloramphenicol, fluconazole is not associated with severe adverse effects following

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in American Journal of Veterinary Research

studies 7 8 9 10 have identified chloramphenicol and fluconazole as drugs that can act as pharmacokinetic enhancers of methadone in dogs, presumably through CYP inhibition. Fluconazole increases methadone's oral bioavailability 98− to 176-fold and

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in American Journal of Veterinary Research

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).

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in American Journal of Veterinary Research