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J. Zhang, L. Wang, X. Li, T. Zhou, H. Xia; Ocular Pharmacokinetics and Bioavailability of Topically Applied Voriconazole Solution Containing Hydroxypropyl Beta-Cyclodextrin to Rabbits. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5959.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate an aqueous voriconazole (VOR) eye drop in order to increase the corneal permeability and improve ocular bioavailability following topical application.
Hydroxypropyl beta-cyclodextrin (HP-β-CD) was used to formulate an aqueous eye drop to improve aqueous solubility of VOR. A single dose of either VOR suspension (0.5%) (VOR-SP) or VOR (0.5%)/HP-β-CD solution VOR-CD) was applied to rabbits. The aqueous humor and cornea were collected after 5,10,20,30,45,60,90 and 120min. VOR concentrations in aqueous humor and corneas were determined by HPLC after extraction.
After topically applying VOR-CD, the VOR concentrations in aqueous humor were 10.83±2.99, 11.37±3.52, 6.22±0.75, 2.89±0.71, 2.07±0.53, 0.86±0.22, 0.30±0.11 and 0.18±0.09µg/ml at 5~120min, significantly higher compared with those of VOR-SP at the corresponding time points (p < 0.05). The half-lives (t1/2) of VOR in aqueous humor for VOR-CD and VOR-SP were 37 and 20 min, respectively. The VOR-CD produced an over 1.7-fold bioavailability (AUC0-120, area under the concentration-time curve between 0 and 120 min) increase in aqueous humor over the VOR-SP. Peak VOR concentration in cornea (43.09±11.83 µg/g) was achieved within 5 min after instillation of VOR-CD, the VOR concentrations in cornea were 43.09±11.83, 41.90±7.86, 36.08±23.38, 14.02±11.29, 25.63±15.92, 29.64±11.96, 26.22±8.11 and 17.13±8.48µg/g at 5~120min, respectively, and were 2.2, 2.6, 4.9, 4.7, 1.7, 3.9, 6.0 and 4.0 times higher than those of VOR-SP at the corresponding time points, respectively. The half-lives (t1/2) of VOR in cornea for VOR-CD and VOR-SP were 241 and 298 min, respectively. The VOR-CD produced an 3.5-fold bioavailability (AUC0-120) increase in corneas over the VOR-SP.
VOR-CD is superior to VOR-SP by increasing corneal peneteration and ocular bioavailability.
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