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Hai Tang, Xin Zhao, Xu Shen, Xian Zhang, Shichao Chen, Yang Tong, Hong Lu; Ocular pharmacokinetics of Natamycin after a single or repeated ocular instillation in rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5402.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the ocular pharmacokinetics of Natamycin (Nat) after a single or repeated topical instillation in Japanese white rabbit using simplified liquid chromatography - tandem mass spectrometry (LC-MS-MS).
36 healthy rabbits were randomly divided into 2 groups. For the single dosing group (30), a 50μl of 5% Nat was instilled into the left eyes and each group was divided evenly into six subgroups. From each subgroup, the animals were sacrificed at 5, 10, 15, 30, 60 and 90mins after the instillation immediately to collect aqueous humor and corneas. For the repeated dosing group (6), a 50μl of 5% Nat was instilled into the left eyes every hour for 12 hours during the day time, the animals were treated a single group. The concentration of Nat was measured by LC-MS-MS.
The LC-MS-MS methods allowed Nat quantification as low as 2.0ng/ml (R>0.99), respectively, for up to 90mins after a single administration of Nat to the eye.After a single topical instillation, Nat reached the highest concentration in cornea at 10mins (Cmax:299.3ng/g). Nat was detected at all selected time points in the aqueous humor, and the highest was 27.03ng/ml at 30mins. The repeated dosing group, the concentrations in cornea and aqueous humor for Nat were 10569ng/g and 54.4ng/ml, respectively.
Our simplified method achieved the required sensitivity and specificity for a pharmacokinetic study in rabbit specimens after a single or repeated topical administration of Nat. After the repeated administration, the high-level distribution of Nat was only observed in the cornea, and the poor corneal penetration of Nat suggests that it is more suitable for superficial corneal fungal infections.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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