prostaglandin-f2-isopropyl-ester and Hyperemia

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.

Topics: Adolescent; Adult; Aqueous Humor; Dinoprost; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Evaluation Studies as Topic; Glaucoma; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Male; Ophthalmic Solutions; Prostaglandins F, Synthetic

A study was carried out to assess the clinical efficacy of PhXA41, a new phenyl-substituted prostaglandin F2 alpha-isopropyl ester analogue, using a single administration in 35 subjects with ocular hypertension or primary open-angle glaucoma. PhXA41 caused a dose-dependent intraocular pressure (IOP) reduction which continued 24 hours or more after administration. The mean IOP reduction 8 hours after treatment compared with the baseline IOP was 3.4, 4.9 and 5.9 mmHg for the doses of 25, 50 and 100 micrograms/ml, respectively. Although slight conjunctival hyperemia occurred in some patients, it disappeared by the next day with no treatment. No aqueous flare or cells were detected, no significant change in pupillary diameter was found, and no systemic symptom was reported. Thus, PhXA41 was well tolerated in subjects with ocular hypertension or primary open-angle glaucoma. Furthermore, its IOP-reducing effect was so long-lasting that a once daily application may suffice for clinical use.

Topics: Adult; Aged; Conjunctiva; Dinoprost; Dose-Response Relationship, Drug; Drug Tolerance; Female; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic

Ocular hypotensive effects and side effects of two different topically applied prostaglandin (PG) esters were evaluated in a double masked study in 12 healthy males. Three doses of 15-propionat-PGF2 alpha-isopropylester (15-prop-PGF2 alpha-IE), two doses of PGF2 alpha-isopropylester (PGF2 alpha-IE), and placebo were compared. At equipotent doses 15-prop-PGF2 alpha-IE caused similar ocular side effects as PGF2 alpha-IE. It is concluded that both PGF2 alpha-IE and 15-prop-PGF2 alpha-IE reduce the IOP in normal eyes, but the use of a diester such as 15-prop-PGF2 alpha-IE does not provide a better separation between effect on IOP and side effects than PGF2 alpha-IE.

Topics: Administration, Topical; Adult; Dinoprost; Double-Blind Method; Drug Evaluation; Humans; Hyperemia; Intraocular Pressure; Male; Ocular Hypotension

The effects of PGF2 alpha-isopropylester eye drops on intraocular pressure (IOP) and aqueous humour dynamics were investigated in healthy male volunteers. The other eye was treated with vehicle and used as a control. Special attention was also paid to adverse effects. Single and repeated doses were tested. There was a dose related effect on IOP. Significant reductions were observed 4, 8, and 12 hours after application of 1.0, 2.5, or 10 micrograms PGF2 alpha equivalents of the drug. With 10 micrograms the effect lasted 24 hours. An initial tendency towards an increase in IOP was observed for these doses. Repeated doses of 1.0 microgram daily or 0.5 microgram twice daily produced a significant and lasting IOP reduction of about 2 mmHg for 1-2 weeks. Aqueous humour production was not altered, and outflow facility was not significantly changed. There was a dose dependent hyperaemia with a maximum within 2 hours after application. A foreign body sensation, some pain, and photophobia were noted with increasing doses. A slight miosis of 1 mm was seen in three of six eyes treated with 10 micrograms. No signs of intraocular inflammation were recorded, but a slight increase in penetration of fluorescein into the anterior chamber was observed after 16 days of treatment.

Topics: Adult; Aqueous Humor; Dinoprost; Dose-Response Relationship, Drug; Eye; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions

In a randomized, double-masked, placebo-controlled study, 0.25 microgram (n = 11) or 0.5 microgram (n = 13) of prostaglandin F2 alpha-1-isopropyl ester (PGF2 alpha-IE) was applied topically twice daily for 8 days to one eye of ocular hypertensive or chronic open-angle glaucoma patients. Compared with contralateral, vehicle-treated eyes, PGF2 alpha-IE significantly (P less than 0.05) reduced intraocular pressure (IOP), beginning 4 hours after the first 0.5-microgram dose and lasting at least 12 hours after the fourteenth dose, with a significant (P less than 0.005) mean reduction of 4 to 6 mmHg maintained throughout the last day of therapy with either dose. A contralateral effect was not observed. Mean tonographic outflow facility was significantly (P less than 0.05) higher in PG-treated compared with vehicle-treated eyes (0.17 +/- 0.02 versus 0.12 +/- 0.01 microliter/minute/mmHg, respectively; +/- standard error of the mean) for the 0.5 microgram dose. Conjunctival hyperemia reached a maximum at 30 to 60 minutes after PGF2 alpha-IE application. Some patients reported mild irritation lasting several minutes after some doses. Visual acuity, accommodative amplitude, pupillary diameter, aqueous humor flare, anterior chamber cellular response, Schirmer's test, pulse rate, and blood pressure were not significantly altered. Our findings show that PGF2 alpha-IE is a potent ocular hypotensive agent and a promising drug for glaucoma therapy.

Topics: Aged; Conjunctiva; Dinoprost; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Patient Compliance; Random Allocation; Tonometry, Ocular

One and 2 micrograms of prostaglandin F2 alpha isopropyl ester (PGF2 alpha -IE) applied topically to the rabbit eye caused a biphasic response. The hypotensive phase was dose-dependent with a maximum reduction in intraocular pressure (IOP) of 9.4 +/- 1.7 mmHg at a dose of 2 micrograms. In beagles, 0.4 to 2 micrograms topical PGF2 alpha-IE resulted in a sustained IOP reduction; 2 micrograms produced the maximum reduction of 7-9 mmHg. No initial hypertensive response was observed. Iloprost phenacyl ester (Iloprost-PE) caused a greater decrease in IOP when dissolved in 0.5% hydroxypropyl methylcellulose (AT) than in saline. In rabbits, doses of 0.1 to 1 microgram in AT caused a biphasic response with a sustained IOP decrease fluctuating between 7 and 8 mmHg. In beagles 1 and 2 micrograms Iloprost-PE resulted in a mean IOP reduction of 5.8 +/- 0.4 mmHg and 5.8 +/- 0.5 mmHg (P less than 0.005), respectively; the decrease persisted for 5 hrs. No initial hypertensive response was observed. In beagles PGF2 alpha-IE induced a strong miosis lasting more than 6 hours; Iloprost-PE had no effect on pupil size. Both PG-esters induced a slight hyperemia in rabbit and beagle eyes. In rabbits Iloprost-PE affects the blood-aqueous barrier more than PGF2 alpha-IE, since higher protein concentrations are seen in the aqueous humor after application of Iloprost-PE. Neither PG-ester had a noticeable effect on aqueous protein in beagles. In rabbits, both PG-esters led to slightly increased aqueous humor cyclic-AMP concentrations. In beagles aqueous humor cyclic-AMP was elevated only after Iloprost-PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Animals; Aqueous Humor; Cyclic AMP; Dinoprost; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Hyperemia; Hypromellose Derivatives; Iloprost; Intraocular Pressure; Methylcellulose; Pupil; Rabbits; Time Factors; Tonometry, Ocular