Topically applied aminocaproic acid concentrates in the aqueous humor of the rabbit in therapeutic levels.

Abstract

Systemically administered aminocaproic acid, used to reduce the incidence of secondary hemorrhage in traumatic hyphema, has been shown to accumulate in the aqueous humor of rabbits in a dose-dependent manner. Eight topical preparations of aminocaproic acid were studied to determine aqueous humor concentrations. The vehicles studied included the following: sodium chloride, 0.85 g/dL; polyvinyl alcohol, 1.4 g/dL; hydroxypropyl methylcellulose, 0.4 g/dL; benzalkonium chloride, 0.01 g/dL; ethylenediamine tetraacetic acid disodium, 0.01 g/dL; dimethyl sulfoxide, 11 and 39.6 g/dL; and carboxypolymethylene, 4 g/dL. All contained 735 g/L of aminocaproic acid except for dimethyl sulfoxide (39.6 g/dL) and carboxypolymethylene (4 g/dL), which contained 238 and 600 g/L of aminocaproic acid, respectively. Aqueous humor and plasma samples were assayed for aminocaproic acid content following topical administration. Aqueous humor concentrations of aminocaproic acid ranged from undetectable (less than 0.01 mg/dL) to 5.75 mg/dL. Plasma concentrations ranged from undetectable (less than 0.01 mg/dL) to 9.85 mg/dL. Polyvinyl alcohol (1.4 g/dL) and carboxy polymethylene (4 g/dL) provided the highest aqueous humor aminocaproic acid concentrations. The aqueous humor levels with topical aminocaproic acid administration were comparable with those achieved by systemic administration. Plasma drug levels with topical aminocaproic acid were between 5% and 33% of levels achieved by systemic aminocaproic acid. This study demonstrates that aminocaproic acid can be effectively delivered into the anterior chamber of rabbits by topical application.