Allan Kupferman

Evaluation of Dexamethasone Acetate as a Topical Ophthalmic Formulation

Penetration of an ophthalmic suspension of 0.1% dexamethasone acetate into the rabbit cornea and aqueous humor was unaffected by the status of the corneal epithelium or by the presence or absence of intraocular inflammation. However, the total quantity of this corticosteroid that could be measured in the cornea or aqueous humor was significantly less than that produced by either dexamethason alcohol or dexamethasone sodium phosphate. Despite this, dexamethasone acetate was the most effective of the three dexamethasone derivatives in suppressing inflammation in the cornea, which indicates that following topical administration to the eye it is the most potent of the dexamethasone derivatives studied. This greater therapeutic effect does not seem to be accompanied by a greater propensity to increase intraocular pressure. Comparison of the intraocular pressureincreasing effect in known corticosteroid responders of dexamethasone acetate with that of dexamethasone sodium phosphate, the least effective of the dexamethasone products studied, demonstrated no difference between the two drugs. These data support the conclusion that dexamethasone acetate is superior to the commercially available dexamethasone derivatives for use as a topical ocular anti-inflammatory agent.

Penetration of Fluorometholone Into the Cornea and Aqueous Humor

In each of the experimental conditions studied, fluorometholone penetrated into the cornea and aqueous humor following topical administration of a standard drop. The amount of drug measured in each location was less than that previously documented for dexamethasone and prednisolone preparations. In contrast to these more conventional steroids, the ocular penetration of fluorometholone appeared to be unaffected by the presence or absence of the corneal epithelium or of intraocular inflammation.

Penetration of topically administered prednisolone acetate into the human aqueous humor.

A single standardized drop of 1.0% prednisolone acetate labeled with tritiated thymidine was administered topically to one eye of 58 patients shortly before elective cataract extraction. An aqueous humor sample was aspirated at varying intervals and its corticosteroid content was determined. Peak drug concentration in aqueous humor was 1.13 mug/ml, which occurred 30 to 45 minutes after instillation of the medication. Substantial quantitites of corticosteroid were found in the aqueous humor five minutes after drug administration. The area under the drug concentration in aqueous humor-vs-time curve (a measure of the drugs bioavailability in aqueous humor) was 88 mug min/ml, and its half-life in human aqueous humor was 28 minutes. None of these values were significantly different from the comparable values in rabbit eyes.

Biological Equivalence of Ophthalmic Prednisolone Acetate Suspensions

We compared both concentrations (0.125 and 1.0%) of two widely used commmerical brands of prednisolone acetate suspensions. We investigated the concentration that each product attained in the cornea and aqueous humor, and each products anti-inflammatory effectiveness in the cornea. There was no statistically significant difference in the corticosteroid levels measured in cornea or aqueous humor after administration of the two suspensions. Similarly, there was no significant difference in the ability of the two commercial preparations to suppress corneal inflammation.