Clinical efficacy of PhXA34 and PhXA41, two novel prostaglandin F2 alpha-isopropyl ester analogues for glaucoma treatment.
Four clinical studies were performed in 54 healthy Japanese volunteers to assess the efficacy and the safety of two phenyl-substituted PGF2 alpha-isopropyl ester analogues, PhXA34 and PhXA41 after both single and repeated administrations. PhXA34 and PhXA41 reduced intraocular pressure (IOP) significantly in a dose-dependent way. The maximum IOP reductions were 14.5% to 17.5% with baseline adjustment at 10 to 12 hours after a single administration. No transient early elevation in IOP after treatment was observed. Based on the maximum IOP reducing effect of 1 microgram of PhXA34 and PhXA41, PhXA41 appeared to be at least 1.5 times more active than PhXA34. Tachyphylaxis of the ocular hypotensive effect did not develop during repeated administration for 5 days. A mild conjunctival hyperemia occurred in some subjects at high doses; it tended to diminish with time during the repeated administration of both drugs. Neither PhXA34 nor PhXA41 caused any change at any time in the aqueous flare intensity measured with a laser flare-cell meter. There were no changes in pupillary diameter after treatment. Each drug was well tolerated and caused no other ocular or systemic side effects.
Hotehama
Y
Y
Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
Mishima
H K
HK
D000293:Adolescent; D000328:Adult; D001082:Aqueous Humor / Q000378:metabolism; D015237:Dinoprost / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005069:Evaluation Studies as Topic; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*
D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; C041158:prostaglandin F2 isopropyl ester; D000077338:Latanoprost; D015237:Dinoprost