Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics1,

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Abstract

PURPOSE: To determine the mechanism of intraocular pressure lowering for the Ocular Hypotensive Lipid, AGN 192024 (Allergan, Inc, Irvine, California).

METHODS: Twenty-five normal human volunteers between the ages of 21 and 48 took part in a randomized, double-masked, placebo-controlled, paired-comparison study in which intraocular pressure, aqueous humor flow, and tonographic resistance to outflow were studied. Measurements of aqueous flow were made during the day and at night while subjects slept. Intraocular pressure was measured with the Goldmann tonometer, and resistance to outflow was measured by electronic recording Schiötz tonography.

RESULTS: Intraocular pressure was decreased by 20% on day 3 in AGN 192024-treated eyes in comparison with placebo-treated eyes in normal subjects (P < .001). Aqueous humor flow was stimulated 13% during the day (P = .007) and 14% at night (P = .014) by the drug. Tonographic resistance to outflow was decreased 26% by AGN 192024 (P < .001), and apparent resistance to outflow (the ratio of intraocular pressure to aqueous flow) was decreased 31% (P < .001). Assuming that AGN 192024 does not cause prolonged lowering of episcleral venous pressure, the results show that pressure-insensitive outflow is enhanced by 50%, whereas tonographic facility of outflow (reciprocal of resistance) was enhanced 35%.

CONCLUSIONS: AGN 192024 is an ocular hypotensive agent that works by enhancing both pressure-sensitive and pressure-insensitive aqueous humor outflow without diminishing aqueous humor formation.

Section snippets

Subjects and methods

Twenty-seven normal human subjects who met all the entry criteria were entered into the study. Two of these subjects were dropped from the study for a technical reason (fluorescein concentration out of range of fluorophotometer). The other 25 subjects completed all aspects of the study, and their results are reported here.

The most important inclusion criteria were as follows: normal healthy volunteer, age 21 or older, intraocular pressure inclusive between 12 and 21 mm Hg in both eyes,

Results

The mean age of the 25 subjects who completed the study was 34 years (range, 21 to 48). Twelve of these subjects were men, and 13 were women. The depth of the anterior chamber and the corneal diameter were similar in the study eyes and the control eyes. This subjective finding was confirmed by mean measurements (± SD) of the volume of the anterior chambers: 204 ± 37 μl for the drug-treatment designated eyes and 206 ± 37 μl for the placebo-treatment designated eyes. The mean difference in

Discussion

The clinical studies of AGN 192024 have shown that its ocular hypotensive effects after a single dose last many hours.4 The long steady-state that AGN 192024 produces makes it easy to study its physiologic effects, because there is ample time during which to measure aqueous flow. Thus, a lapse of time between pressure and flow measurements is not critical.

It was noted that the intraocular pressure in the placebo-treated eyes on days 2 and 3 was 10% to 11% lower than on day 1 (baseline) before

References (12)

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This study was supported in part by National Institutes of Health research grant (EY 00634; Dr Brubaker), Bethesda, Maryland; Allergan, Inc, Irvine, California; Research to Prevent Blindness, Inc, New York, New York; and the Mayo Foundation, Rochester, Minnesota.

1

Accelerated publication.

2

Dr Brubaker is a consultant for Allergan. Drs Carpenter and VanDenburgh and Ms Chen are employees of Allergan.

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