Corneal Permeability of Aldose Reductase Inhibitor, M79175. II. In vivo Study on Pharmacokinetic Aspect

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Abstract
Transcorneal permeability of M79175 was estimated in vivo and the effects of pH and thickening agent on it were examined. The aqueous humor concentration of M79175 versus time profile showed the peak concentration of 850 ng/ml at 20 min after instillation of pH 7.0 eye drop solution. The permeability constant of M79175 was estimated by applying a physiologically based pharmacokinetic model to this profile. As was expected from the results in vitro, high permeability constant was observed in vivo. Lowering the pH of the solution demonstrated the tendency to decrease the concentration at 20 min. Thickening agent, Hydroyethylcellulose, did not change the aqueous humor concentration versus time profile. Ocular tissue distribution was examined using 14C-M79175. As was expected from the results of corneal permeability, high levels of M79175 accumulated to the lens.