EFFECTS OF PHXA41, A NEW PROSTAGLANDIN-F(2-ALPHA) ANALOG, ON AQUEOUS-HUMOR DYNAMICS IN HUMAN EYES

Purpose: PhXA41, a new phenyl-substituted analog of a prostaglandin F2 alpha (PGF2alpha) prodrug 14-dihydro-17-phenyl-18,19,20-trinor-prostag landin F2alpha-1-isopropyl ester), is an effective ocular hypotensive agent in patients with glaucoma. To understand its mechanism of action , various components of aqueous humor dynamics were examined after top ical application to human eyes. Methods: In a randomized, double-maske d, placebo-controlled study, PhXA41 (0.006%) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension o r ocular hypertension. The other eye was similarly treated with vehicl e. Intraocular pressure (IOP) was measured by pneumatonometry and tono graphic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluoropho tometric technique, and uveoscleral outflow was calculated secondarily . Comparison of values obtained in treated versus contralateral contro l eyes and on baseline versus day 8 of treatment were made. Results: C ompared with baseline measurements, PhXA41 significantly (P < 0.001) r educed IOP by 5.5 +/- 0.6 mmHg (mean +/- standard error of the mean) a s measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric out flow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 +/- 0.22 m ul/minute) compared with either the contralateral vehicle-treated eyes (0.14 +/-0.30; P < 0.02) or baseline measurements (0.39 +/- 0.20 mul/ minute; P < 0.05). Conclusions: PhXA41 decreases IOP in humans by incr easing uveoscleral outflow without significantly affecting other param eters of aqueous humor dynamics.