Effects of PhXA41, a new prostaglandin F2 alpha analog, on aqueous humor dynamics in human eyes.
OBJECTIVE
PhXA41, a new phenyl-substituted analog of a prostaglandin F2 alpha (PGF2 alpha) prodrug (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-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 topical application to human eyes.


METHODS
In a randomized, double-masked, placebo-controlled study, PhXA41 (0.006%) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension or ocular hypertension. The other eye was similarly treated with vehicle. Intraocular pressure (IOP) was measured by pneumatonometry and tonographic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluorophotometric technique, and uveoscleral outflow was calculated secondarily. Comparison of values obtained in treated versus contralateral control eyes and on baseline versus day 8 of treatment were made.


RESULTS
Compared with baseline measurements, PhXA41 significantly (P < 0.001) reduced IOP by 5.5 +/- 0.6 mmHg (mean +/- standard error of the mean) as measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric outflow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 +/- 0.22 microliter/minute) compared with either the contralateral vehicle-treated eyes (0.14 +/- 0.30; P < 0.02) or baseline measurements (0.39 +/- 0.20 microliter/minute; P < 0.05).


CONCLUSIONS
PhXA41 decreases IOP in humans by increasing uveoscleral outflow without significantly affecting other parameters of aqueous humor dynamics.
Toris
C B
CB
Department of Ophthalmology, University of Nebraska Medical Center, Omaha 68198-5540.
Camras
C B
CB
Yablonski
M E
ME
D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D015590:Fluorophotometry; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use*; D014065:Tonometry, Ocular
D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost