Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing

Passler, N. H.; Chan, H. M.; Stewart, Allison J.; Duran, Sue H.; Welles, Elizabeth G.; Lin, Hui; Ravis, William R.

doi:10.1111/j.1365-2885.2009.01099.x

Cited by 20 publications

(14 citation statements)

References 35 publications

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“…In contrast, none of our patients presented with cerebral mycosis. Studies of chickens and horses revealed remarkable interspecies differences in tissue penetration of VRC (2,4,20). In rats, free extracellular lung concentrations reached ϳ2.5 g/ml after a single dose (13).…”

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confidence: 99%

Human Tissue Distribution of Voriconazole

Weiler

Fiegl

MacFarland

et al. 2011

Antimicrob Agents Chemother

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Voriconazole concentrations were determined in autopsy samples of eight patients who had been treated for a median of 7 days (interquartile range [IQR], 5 days). Voriconazole penetrates well into various tissues, with median levels of 6.26 μg/g ((interquartile range [IQR], 7.87 μg/g) in the lung, 3.41 μg/g (IQR, 16.72 μg/g) in the brain, 6.89 μg/g (IQR, 24.16 μg/g) in the liver, 6.47 μg/g (IQR, 6.19 μg/g) in the kidneys, 5.60 μg/g (IQR, 11.49 μg/g) in the spleen, and 7.55 μg/g (IQR, 16.91 μg/g) in the myocardium.

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confidence: 99%

Human Tissue Distribution of Voriconazole

Weiler

Fiegl

MacFarland

et al. 2011

Antimicrob Agents Chemother

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“…Continuous infusion of the drug may result in efficacy with a lesser dosage as with intermittent therapy of topical voriconazole. The contribution from crossover of the 5 mg of voriconazole from the SCo injection 48 h prior to euthanasia to the contralateral eye at 2 h was considered negligible based on the estimated percentage of voriconazole that reaches the eye following systemic administration [52][53][54]. However, the fact that voriconazole plasma concentrations were not measured after SCo injection was a limitation of the study.…”

Section: Discussionmentioning

confidence: 99%

“…A priori power calculations were performed using GPower v.3.1.9.2 to estimate the number of horses required for the study. Using a type 1 error of 0.05, a type 2 error of 0.8 and an estimated effect size of 1.4 (based on the mean and standard deviation of previous studies measuring voriconazole in AH [4,54]), it was determined that 5-7 horses were needed per group. A total of 12 horses were included in the study, 6 for the first aim and 6 for the second aim.…”

Section: Animalsmentioning

confidence: 99%

“…Phosphate-buffered saline samples were analyzed by reverse phase high performance liquid chromatography (HPLC) as described elsewhere [34,54,66]. The HPLC system (Agilent 1200 series) encompassed pumps, autosampler, UV and visible light absorption detector, column (Thermo BetaBasic-18, 4.6 mm × 15 cm, 5 μ; Bellefonte, PA, USA), and computer interface.…”

Section: Determination Of Voriconazole Concentrationsmentioning

confidence: 99%

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Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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Background: Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes. Results: Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment. Conclusions: Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.

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“…Although itraconazole is reported to have high oral bioavailability in the horse, this does "not" apply to the compounded formulation but only to the Sporanox ® solution (Janssen Pharmaceutica NV, Olen, Belgium). A recent study determined that voriconazole is well distributed to multiple body fluids, including the PELF, after a daily oral dose of 4 mg/kg bwt, and it has been reported to have been used in the successful treatment of invasive pulmonary aspergillosis in a foal [29,30]. Fluconazole has good penetration into equine plasma; however, its penetration into respiratory secretions and tissues has not been determined in horses [28].…”

Section: Treatmentmentioning

confidence: 99%