The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes.
OBJECTIVE
To study the effects of a topically applied prostaglandin F2 alpha analogue, PhXA41 (Latanoprost; 13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-isopropyl ester), on aqueous dynamics in the human eye.


METHODS
A randomized, double-masked study was carried out on 20 normal and 20 ocular hypertensive humans. One eye of each subject was treated with 0.006% PhXA41, while the contralateral eye received placebo twice daily for 5 days.


RESULTS
Compared with placebo, PhXA41 reduced intraocular pressure in both groups by approximately 20%.


RESULTS
Tonographic facility of outflow was increased 24% in the normal group and 30% in the ocular hypertensive group; no changes were observed in the rates of aqueous humor flow in either group. The changes in tonographic facility were insufficient to fully explain the ocular hypotensive effect of the drug, suggesting that PhXA41 enhances outflow via the uveoscleral pathway. The suitability of fluorophotometry as a measure of flow was confirmed by three methods of comparing blood-aqueous barrier permeability: polarization of cameral fluorescence, intensity of backscattered light from the anterior chamber (flare), and cameral fluorescence after oral administration of fluorescein sodium. All of these measured parameters were normal, suggesting that this compound has no clinically significant effects on the blood-aqueous barrier or on the accuracy of fluorophotometry. PhXA41 was well tolerated in both groups. Only four of 40 subjects reported a transient foreign-body sensation, and only one of 40 subjects was observed to have greater than moderate conjunctival hyperemia. Most subjects had no symptoms and no measurable hyperemia.


CONCLUSIONS
These results suggest that PhXA41 is a potentially useful ocular hypotensive agent that enhances the egress of aqueous humor via both major outflow pathways. The relative lack of ocular side effects in this study further suggests that this agent has promise for the treatment of chronic glaucoma.
Ziai
N
N
Department of Ophthalmology, Mayo Clinic, Rochester, Minn.
Dolan
J W
JW
Kacere
R D
RD
Brubaker
R F
RF
D001082:Aqueous Humor / Q000378:metabolism*; D001693:Biological Transport, Active; D002463:Cell Membrane Permeability; D015237:Dinoprost / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004361:Drug Tolerance; D015590:Fluorophotometry; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D015237:Dinoprost