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Abstract #23840 Published in IGR 11-2
Route of penetration of topically instilled nipradilol into the ipsilateral posterior retina
Mizuno K; Koide T; Shimada S; Mori J; Sawanobori K; Araie MInvestigative Ophthalmology and Visual Science 2009; 50: 2839-2847
PURPOSE: To investigate how topically instilled nipradilol penetrates the ipsilateral posterior retina-choroid in normal rabbit eyes. METHODS: Albino rabbits were used. Topical instillation (1%, 100 microL) or intracameral (0.1%, 100 microL) or sub-Tenon injection (0.1%, 10 microL) of [(14)C]nipradilol was performed in one eye. Ocular and periocular distribution and the concentrations of [(14)C]nipradilol were determined by whole-head autoradiography, the results of which were validated by measurements in isolated tissues. In addition, the unchanged form of nonradiolabeled nipradilol in the posterior retina after topical instillation (1%, 100 microL) was quantified by liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS: Autoradiography revealed that the nipradilol concentration after topical instillation was higher in the ipsilateral posterior retina-choroid than on the contralateral side (142.9 ng/g vs. 108.3 ng/g, P = 0.026), and in the periocular tissue around the optic nerve insertion on the ipsilateral side than on the contralateral side (207.1 ng/g vs. 141.1 ng/g, P < 0.001). After intracameral injection, radioactivity was observed only in anterior, but not posterior parts of the eye. Radioactivity was observed only in the ipsilateral posterior retina-choroid and periocular tissues around the optic nerve insertion after sub-Tenon injection. The results in the isolated tissues validated autoradiographic evaluations. CONCLUSIONS: These results suggest that diffusion from posterior periocular tissues across the posterior sclera may be the main route for local penetration of the instilled drug to reach the posterior retina-choroid in albino rabbits.
Department of Pharmacology, Tokyo Research Laboratories, Kowa Co, Ltd, Tokyo, Japan.
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)