Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics.
OBJECTIVE
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.
Brubaker
R F
RF
Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. richard@mayo.edu
Schoff
E O
EO
Nau
C B
CB
Carpenter
S P
SP
Chen
K
K
Vandenburgh
A M
AM
D000328:Adult; D000577:Amides; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001082:Aqueous Humor / Q000378:metabolism*; D000069580:Bimatoprost; D002940:Circadian Rhythm / Q000187:drug effects; D003008:Cloprostenol / Q000031:analogs & derivatives; D004311:Double-Blind Method; D005260:Female; D015590:Fluorophotometry; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008055:Lipids / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D014065:Tonometry, Ocular
D000577:Amides; D000959:Antihypertensive Agents; D008055:Lipids; D009883:Ophthalmic Solutions; D003008:Cloprostenol; D000069580:Bimatoprost