fluprostenol and Glaucoma

To assess the ocular hypotensive effect of 15-keto fluprostenol, the oxidized metabolite of travoprost, on glaucoma patients, through a randomized double-masked placebo-controlled study.. Twelve patients with ocular normal tension glaucoma (NTG) (intraocular pressure [IOP] < 22 mmHg) were enrolled. In order to ensure patient compliance to treatment, all study subjects were hospitalized. In each patient, the eye to be submitted to the treatments was randomly chosen. After hospital admission (day 1), those patients received for 5 days at 8 P.M. either one drop of 15-keto fluprostenol (35 μg/ml) or one drop of placebo. IOP evaluation was performed within 8 A.M. and 8 P.M. for 6 days. Furthermore, we performed a determination of cardiovascular parameters before and after the treatments.. Starting with the first IOP measurement after the first treatment (8 A.M. on day 2), IOP was reduced of about 14% in the eyes treated 15-keto fluprostenol, in comparison with baseline IOP values of 15-keto fluprostenol-treated patients. The IOP reduction in the 15-keto fluprostenol-treated group was significantly compared to placebo group (p < 0.05) starting from day 3 till day 6 of the study. Except for mild hyperemia in one 15-keto fluprostenol-treated eye, no other side effects were observed or reported by the enrolled patients.. The travoprost metabolite 15-keto fluprostenol was effective in decrease IOP and maintained IOP reduction along 5 days of treatment. The 15-keto fluprostenol can be developed as a good candidate for once-a-day NTG patients' treatment.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Prostaglandins F, Synthetic; Treatment Outcome

FP-Class prostaglandin analogs have demonstrated utility for the treatment of glaucoma and ocular hypertension. A series of novel FP prostaglandin analogs was designed to optimize topical ocular activity and reduce ocular side-effects by replacing 13-carbon with oxygen. A facile synthesis was successfully developed for synthesis of the 13-oxa prostaglandins from the commercially available Corey aldehyde benzoate. Among the compounds synthesized, AL-16082 was the most potent prostaglandin FP agonist in vitro. In a prostaglandin FP receptor-linked second-messenger assay, phosphoinositide (PI) turnover, it exhibited a potency value (EC(50)) of 1.9 nM (78% max. response relative to fluprostenol). The isopropyl ester of AL-16082, compound AL-16049, significantly lowered intraocular pressure (IOP) in the ocular hypertensive monkey eyes by 30%. In the study of acute ocular irritation response in New Zealand albino rabbits, AL-16049 produced lower incidence of hyperemia, swelling, and discharge than PGF(2alpha) (1 microg), and a similar incidence of hyperemia, swelling, and discharge to latanoprost (1.8 microg). AL-16049 also produced no signs of ocular irritation or discomfort in the cat at the doses evaluated.

Topics: Administration, Topical; Animals; Cats; Dinoprost; Drug Discovery; Eye Diseases; Glaucoma; Haplorhini; Hypertension; Intraocular Pressure; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Rabbits; Structure-Activity Relationship