dinoprost and Ocular-Hypertension

Optic nerve and retinal diseases such as glaucoma, age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are significant public health concerns and have a momentous impact on patients' functional status and quality of life. These diseases are among the most common causes of visual impairment worldwide and account for billions of dollars in healthcare expenditures and lost productivity. The importance of adequate treatment of these conditions and the need for efficacious therapeutic drugs cannot be overstated. Unoprostone continues to be developed as a potential treatment for these debilitating diseases.. This review provides background information on unoprostone isopropyl (unoprostone), a prostanoid and synthetic docosanoid approved for the treatment of open-angle glaucoma and ocular hypertension, and recapitulates safety and efficacy data as it relates to this indication. Additionally, this review describes potential new uses of unoprostone as therapy for dry AMD and RP. A literature search of peer-reviewed publications was performed utilizing PubMed. Searches were last updated on 10 September 2012.. Current data indicate that unoprostone does significantly lower intraocular pressure (IOP) and has a favorable safety and tolerability profile. However, the IOP-lowering effects of unoprostone do not compare with other commercially available prostanoids and it has the disadvantage of a twice-daily rather than once-daily dosing regimen. Nonetheless, recent data suggest that unoprostone may improve neuronal survival and increase ocular blood flow, indicating that it may have some value as a therapy for glaucoma, RP and dry AMD. Further studies are needed to confirm whether unoprostone provides any clinically significant advantage over the other commercially available prostanoids.

Topics: Antihypertensive Agents; Dinoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Macular Degeneration; Ocular Hypertension; Retinitis Pigmentosa; Treatment Outcome

It is still uncertain whether travoprost has comparable or better efficacy compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension. The authors performed a meta-analysis of randomized controlled trials to evaluate the incidence of reported side-effects and intraocular pressure (IOP)-lowering effect of travoprost versus other prostaglandin analogues (latanaprost, bimatoprost, unoprostone) or timolol.. Systematic literature retrieval was conducted in Pubmed, EMBASE, Chinese Bio-medicine Database and Cochrane Controlled Trials Register to identify the potentially relevant randomized controlled trials. The statistical analysis was performed by RevMan 4.1 software that was provided by the Cochrane Collaboration. The outcome measures were the incidence of reported side-effects (hyperaemia, iris pigmentation, eyelash changes) and mean IOP pooled over treatment visits.. In total, 12 articles involving 3048 patients with open-angle glaucoma or ocular hypertension were included in this meta-analysis. The combined results showed that travoprost 0.004% was more effective than timolol or travoprost 0.0015% in lowering IOP, but not more effective than bimatoprost or latanoprost. Travoprost 0.004% caused a higher percentage of hyperaemia than timolol, latanoprost, or travoprost 0.0015%. There was an increased incidence of pigmentation with travoprost than timolol. Travoprost 0.004% caused a higher percentage of eyelash changes than timolol, latanoprost, or travoprost 0.0015%.. According to data available, travoprost is more effective than timolol in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Compared with other prostaglandin analogues, travoprost appears to be equivalent to bimatoprost and latanoprost. Although a limited number of local side-effects were reported, no serious treatment-related side-effects were reported.

Topics: Aged; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Lipids; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Timolol; Travoprost

Latanoprost became the first line therapeutic agent in glaucoma treatment being the best sold worldwide anti-glaucoma medication. When adequate intraocular pressure decrease can not be achieved with latanoprost monotherapy, then its combinations are to be used. Latanoprost combinations are grouped in to non-fixed and fixed variants. Non-fixed combinations mean concomitant therapy,that is giving the two or more medications using different bottles. The medications used for latanoprost non-fixed combinations are represented by timolol 0.5%, pilocarpine 2%, acetazolamide dispensed systemically and locally, dipivefrin 0.1%, unoprostone 0.12% and brimonidine 0.2%. Fixed combinations mean administering the two mixed medications using one single bottle. At the present time there is only one fixed combination of latanoprost i.e. its combination with timolol 0.5% whose trading name is Xalcom.

Topics: Acetazolamide; Administration, Topical; Antihypertensive Agents; Brimonidine Tartrate; Dinoprost; Drug Combinations; Drug Therapy, Combination; Epinephrine; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Pilocarpine; Prostaglandins F, Synthetic; Quinoxalines; Timolol

This review summarises the safety of unoprostone isopropyl (both at the 0.12 and 0.15% concentrations) instilled twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). For unoprostone 0.15%, combined data from two 12-month comparative monotherapy studies are reported, as well as data from three adjunctive therapy studies and two special population studies. With unoprostone monotherapy, most adverse events were mild or moderate and transient in nature. Less than 7% of unoprostone-treated patients discontinued therapy due to an adverse event. The most common adverse events associated with unoprostone were burning/stinging, burning/stinging directly upon drug instillation, ocular itching, and conjunctival hyperaemia. Unoprostone had no clinically notable effects on vital signs, laboratory profiles, or comprehensive ophthalmic examinations. One of 659 unoprostone 0.15%-treated patients had a change in iris colour after 12 months of monotherapy. Except for a higher incidence of burning/stinging and burning/stinging upon instillation, unoprostone was comparable to timolol 0.5% twice daily and betaxolol 0.5% twice daily. No safety concerns were raised with use of unoprostone as adjunctive therapy. Unoprostone had no significant effect on exercise-induced heart rate in healthy subjects or on pulmonary function in patients with mild-to-moderate asthma. The safety profile of unoprostone 0.15% was consistent with published information on the 0.12% formulation. In conclusion, unoprostone has an excellent safety profile in patients with POAG or OH.

Topics: Antihypertensive Agents; Chemotherapy, Adjuvant; Demography; Dinoprost; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Ocular Hypertension

Latanoprost, a prostaglandin F(2alpha) analog prodrug, and unoprostone, an analog of a prostaglandin metabolite, have been shown to be effective in decreasing intraocular pressure when used alone or in combination with other ocular hypotensive agents. The increase in the uveoscleral outflow and some of the side effects are probably FP-receptor mediated, which may account for some differences between the cited drugs. This article reviews the recent literature available on the clinical efficacy of these prostanoids, as well as the studies directly comparing these drugs.

Topics: Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic

To review available data related to the use of prostaglandin analogs (bimatoprost, latanoprost, travoprost, unoprostone) in the management of ocular hypertension and open-angle glaucoma.. Primary and review articles were identified from a MEDLINE search (1966-May 2001) and requested information from product manufacturers.. All available information, including that published in articles and abstracts, which was deemed relevant was included in this review. Limited data have been published to date.. The prostaglandin analogs appear to be effective, well-tolerated agents for the reduction of intraocular pressure (IOP) in patients with primary open-angle glaucoma and ocular hypertension. This drug class offers an alternative for patients who do not achieve control with another topical antiglaucoma agent or for those with a contraindication to first-line therapy with beta-adrenergic antagonists. Based on preliminary clinical data, bimatoprost, latanoprost, and travoprost appear to be at least as effective as timolol, while the effectiveness of unoprostone is similar or slightly less. Prostaglandin analogs may be used in conjunction with other antiglaucoma medications, although further studies must establish the optimal combination. Whether clinical experience will yield outcomes in favor of one of the prostaglandin analogs remains to be determined. Patients should be educated on adverse events associated with prostaglandin analogs, particularly the potential for changes in the pigmentation of the iris and eyelashes.. Bimatoprost, latanoprost, and travoprost appear to be equivalent to the current standard of therapy in the topical treatment of elevated IOP. Further clinical data published in article versus abstract format is required to better assess potential differences among these 3 agents.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Drug Storage; Glaucoma, Open-Angle; Humans; Latanoprost; Lipids; Ocular Hypertension; Prostaglandins; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Travoprost

Latanoprost and unoprostone (isopropyl unoprostone) represent the first commercially available prostaglandin analogues to be used for the treatment of glaucoma. Both compounds reduce intraocular pressure by enhancing uveoscleral outflow. Latanoprost, when used once daily in the evening, produces a greater reduction in pressure than timolol. Latanoprost produces mild conjunctival hyperaemia compared with timolol in some patients. Darkening of the irides has been reported, especially in green-brown, yellow-brown and blue/grey-brown irides. Hypertrichosis and hyperpigmentation of the eyelashes have also been demonstrated. Although latanoprost has not been proven to cause uveitis or cystoid macular oedema, case reports of an association exist. Latanoprost does not produce systemic adverse effects nor does it alter routine blood analyses. Unoprostone, when given twice daily, produces less of a reduction in intraocular pressure than timolol or latanoprost. Three times daily use may be required to approach the effectiveness of timolol. Unoprostone may have a similar adverse effect profile to latanoprost, but may to cause more corneal epithelial problems. Unoprostone is also not known to cause systemic adverse effects. Both agents are welcome additions to the treatment of glaucoma. However, additional studies and more experience are needed with each agents.

Topics: Dinoprost; Drug Administration Schedule; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Latanoprost; Ocular Hypertension; Pigment Epithelium of Eye; Prostaglandins F, Synthetic; Risk Assessment

Two prostaglandin molecules have important physiological and pathophysiological role in the tissues of the eye. Prostaglandin F2 alpha takes part in mediating intraocular pressure, prostaglandin E2 is the mediator of inflammation. In case of increased intraocular pressure, latanoprost a derivative of prostaglandin F2 alpha can be applied. Numerous data are available on the favourable intraocular pressure lowering effect of latanoprost. It can be applied as a single hypotensive or it can be combined with eye-drops currently used in glaucoma. It exerts its therapeutic effect by increasing uveoscleral outflow. Inflammation in the eye can be diminished by nonsteroidal anti-inflammatory drugs similarly to inflammations in other tissues of the organism. Literature on nonsteroidal anti-inflammatory drugs is enormous. Molecules of different structures inhibit the synthesis of prostaglandins. Primarily they are useful anti-inflammatory agents, reduce intraocular pressure in secundary glaucoma, inhibit intraocular miosis and prevent development of cystoid macula oedema. Nonsteroidal anti-inflammatory drugs do not exert their effects on prostaglandins themselves, but inhibit their synthesis. Hence the use of both, latanoprost and nonsteroidal anti-inflammatory drugs simultaneously, improves safety of therapy in case of patients prone to uveitis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Dinoprostone; Eye; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ocular Physiological Phenomena; Prostaglandins; Prostaglandins F, Synthetic; Uveitis

To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily.. In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period.. In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey.. Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Cross-Over Studies; Dinoprost; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Quinoxalines; Timolol; Treatment Outcome

To compare the efficacy and safety of unoprostone versus brimonidine both given twice daily in ocular hypertensive or primary open-angle glaucoma subjects.. After a 1-month washout period a baseline diurnal curve was measured every 2 hours from 08:00 hours (trough) to 20:00 hours in subjects with a trough intraocular pressure (IOP) and the pressure 24 mmHg. Qualified subjects were randomized to either brimonidine or unoprostone. After 6 weeks of treatment the period 1 diurnal curve was performed. Subjects were then switched to the opposite treatment for 6 weeks and the period 2 diurnal curve was performed.. A total of 33 subjects were included in this study. In the brimonidine-treated group the trough IOP 20.1 +/- 2.8 mmHg was reduced from baseline up to 8 hours after dosing. In the unoprostone-treated group the trough IOP was 19.5 +/- 3.0 mmHg, which was statistically equal to that of brimonidine (p = 0.21), was reduced from baseline for 12 hours after dosing. Brimonidine decreased the IOP statistically more than unoprostone at 10:00 and 12:00 hours (p < 0.0001 and p = 0.02, respectively), while unoprostone reduced the IOP more than brimonidine at 18:00 and 20:00 hours (p = 0.002 and p = 0.05, respectively). Safety levels were similar between groups, but unoprostone caused more ocular stinging than brimonidine (p = 0.008).. This study suggests that twice daily brimonidine demonstrates a statistically greater peak reduction in IOP than unoprostone. However, unoprostone, but not brimonidine, decreased IOP over the complete 12-hour daytime dosing cycle.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Circadian Rhythm; Cross-Over Studies; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Quinoxalines; Safety; Treatment Outcome

To evaluate the effect of substituting latanoprost(LAT) 0.005% for unoprostone(UNO) 0.12% after a trial of unilateral treatment.. We treated 30 patients with primary open-angle glaucoma(n = 8), ocular hypertension (n = 1), or normal-tension glaucoma(n = 21) with UNO for 4 weeks in one eye and then substituted LAT for UNO. Four weeks later we measured the intraocular pressure(IOP) in the ipsilateral eye.. The mean baseline IOP level was 18.6 +/- 3.8(mean +/- standard deviation) mmHg. The mean IOP levels(reduction rates) after UNO and LAT therapy were 16.7 +/- 3.1 mmHg (16.6%) and 14.1 +/- 3.2 mmHg (28.9%), respectively(p < 0.001). All patients who responded to UNO also responded to LAT; however, 55% of those who did not respond to UNO responded to LAT.. If LAT is substituted for UNO, it can be predicted that 63.3% of the patients will respond.

Topics: Adult; Aged; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; Treatment Outcome

To assess whether iris color and eyelash changes occur with the use of unoprostone for 2 years.. The 2 clinical trials described herein were prospective, randomized, double-masked, active-controlled, parallel group, multicenter studies.. A total of 1131 patients with primary open-angle glaucoma or ocular hypertension participated in 2 clinical trials and received either unoprostone isopropyl 0.15% (659), timolol maleate 0.5% (331), or betaxolol hydrochloride 0.5% (141), 1 drop per eye twice daily for up to 24 months.. Color photographs (1:1 magnification) were taken of the iris and eyelid of each patient at baseline and at regular intervals thereafter through month 24 using a standardized camera system. Photography included 7 views of each eye plus a calibration photograph and a patient identification photograph, for a total of 16 photographs per patient per visit. Two independent (masked) readers subjectively compared baseline iris colors to subsequent visits. Side view photographs of the upper and lower eyelashes were used for the eyelash length analysis, with each having sufficient depth of field and a sufficient number of eyelashes in focus. Similarly, frontal eyelash views were used for the eyelash density analysis.. Changes from baseline in iris color and eyelash length and density within and between treatment groups.. Seven cases of iris color change (1.06%) were confirmed in patients treated with unoprostone for up to 24 months; no confirmed cases were reported in the timolol or betaxolol groups. In the unoprostone group, cases of iris color change were confirmed at months 12 (1 case), 18 (2 cases), and 24 (4 cases). No clinically relevant differences were observed among treatment groups for changes from baseline in eyelash length or density.. Although iris hyperpigmentation and abnormal eyelash changes may occur after treatment with unoprostone, the incidence of these events appears to be low in the 2-year clinical study.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Betaxolol; Dinoprost; Double-Blind Method; Eye Color; Eyelashes; Female; Glaucoma, Open-Angle; Hair Color; Humans; Hyperpigmentation; Incidence; Intraocular Pressure; Iris; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Photography; Timolol

Histological changes of, in particular, collagen and extracellular matrix after administration of topical prostaglandin F(2alpha)(PGF (2alpha)) analogues have been reported. In view of this observation, we investigated the influence of PGF(2alpha) analogues on the central corneal thickness.. In a non-randomized, controlled, cross-sectional study, 403 eyes from 208 consecutive patients were examined: 149 eyes (normals/controls) and 79 with ocular hypertension (OHT), 119 eyes with primary open angle glaucoma (POAG) and 56 eyes with normal tension glaucoma (NTG). One experienced ophthalmologist measured the central corneal thickness (CCT) using ultrasound pachymetry (Tomey AL-2000, sequence of 5 measurements with an SD < 3 microm). The central corneal power was measured with the Zeiss keratometer. Depending on the topical treatment, the patients were classified into 4 groups: A) PGF(2alpha) analogues (n = 78), B) carbonic anhydrase inhibitors (n = 26), C) combination of PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (n = 41), D) none of these drugs (n = 258). T tests and multiple linear regression analyses were used for statistical analysis.. CCT was decreased significantly (p < 0.01 each) in eyes treated with PGF(2alpha) analogues (group A: 529 +/- 34 microM), in comparison with the untreated and non-glaucomatous eyes (part of group D: 542 +/- 35 microM, n = 148), untreated glaucomatous/OHT eyes (part of group D: 563 +/- 37 microM, n = 110), eyes treated with carbonic anhydrase inhibitors (group B: 561 +/- 32 microm) and eyes with a topical application of both PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (group C: 555 +/- 48 microM. No correlation was found between CCT and diagnosis (OHT, POAG, NTG, control), gender, central corneal power, and intraocular pressure in a multivariate analysis.. The present findings suggest that the topical application of prostaglandin F(2alpha) analogues onto the cornea reduces the central corneal thickness significantly. These changes might be attributed to effects of PGF(2alpha) analogues on the extracellular matrix of the corneal stroma via upregulation of matrix metalloproteinases. In clinical practice, corneal thinning under local PGF (2)(alpha) analogue treatment could result in underestimation of intraocular pressure levels as measured by applanation tonometry.

Topics: Acetazolamide; Administration, Topical; Adult; Aged; Carbonic Anhydrase Inhibitors; Cloprostenol; Collagen; Cornea; Corneal Topography; Cross-Sectional Studies; Dinoprost; Drug Therapy, Combination; Extracellular Matrix; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Sulfonamides; Thiophenes; Travoprost; Ultrasonography

To determine the mechanism by which 0.15% unoprostone isopropyl reduces intraocular pressure (IOP) by studying 33 patients with ocular hypertension or primary open-angle glaucoma.. At baseline, IOP was determined by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, episcleral venous pressure by venomanometry, and uveoscleral outflow by mathematical calculation. Unoprostone was administered to one eye and placebo to the fellow eye of each patient twice daily in a randomized masked fashion. In patients who demonstrated an IOP reduction of 3 mm Hg or more in either eye on day 5 +/- 1 (n = 29), determinations were repeated on that day and on day 28 +/- 2. Treated eyes were compared with control eyes, and treatment days were compared with baseline by paired t tests.. Compared with baseline, unoprostone significantly (P<.001) reduced IOP by a mean +/- SEM of 5.6 +/- 0.4 mm Hg and 4.8 +/- 0.6 mm Hg on days 5 and 28, respectively. The change from baseline with unoprostone was significantly (P<.001) greater than with placebo by 2.8 +/- 0.4 mm Hg on day 5 and by 3.2 +/- 0.5 mm Hg on day 28. Compared with baseline, unoprostone significantly (P

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Aqueous Humor; Dinoprost; Double-Blind Method; Female; Fluorophotometry; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Tonometry, Ocular

Impairment of outflow facility in glaucoma causes large intraocular pressure (IOP) fluctuations that have been shown to be a risk factor for disease progression. The water-drinking provocative test (WDT) has been proposed as an indirect measurement of outflow facility to compare intraocular pressure responses of glaucoma eyes to different drugs. This study was a double-masked, randomized, parallel-group clinical trial comparing the IOP fluctuations in response to the WDT in patients using latanoprost versus unoprostone. After completing a wash-out of ocular hypotensive medications, patients with primary openangle glaucoma or ocular hypertension were randomized to receive either latanoprost (N=40) or unoprostone (N=42). IOP was measured before treatment and at 8 weeks after treatment (baseline IOP for WDT), followed by the WDT. IOP fluctuations and maximum IOP after water ingestion were compared between the two groups. Analysis of covariance was used to adjust for the effects of baseline IOP and treatment efficacy. The mean percentage reduction of IOP was 27% in patients using latanoprost, as compared to 13% in patients using unoprostone (p<0.001). Patients on treatment with latanoprost had significantly less IOP fluctuations in response to the WDT, compared to patients using unoprostone. From an overall baseline IOP of 20.0 mmHg and an overall treatment efficacy of 20%, the mean+/-standard error of the mean (SEM) of the IOP fluctuation during the WDT was 5.3+/-0.4 mmHg in the unoprostone group, and 3.6+/-0.4 mmHg in the latanoprost group (p=0.005, ANCOVA). This could represent an additional benefit of latanoprost over unoprostone in controlling the intraocular pressure of glaucomatous patients.

Topics: Antihypertensive Agents; Dinoprost; Double-Blind Method; Drinking; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prostaglandins F, Synthetic; Tonometry, Ocular; Water

To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily.. Prospective multicenter, randomized, double-masked, crossover comparison study.. Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days.. Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial.. This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.

Topics: Antihypertensive Agents; Cross-Over Studies; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Safety; Sulfonamides; Thiophenes; Timolol; Treatment Outcome; Visual Acuity

To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension.. This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy.. Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101).. Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Chemotherapy, Adjuvant; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Quinoxalines; Sulfonamides; Thiophenes; Timolol

To compare the intraocular pressure (IOP)-lowering effect and safety of latanoprost 0.005% once daily with that of unoprostone 0.15% twice daily for patients with primary open-angle glaucoma or ocular hypertension.. Randomized clinical trial.. In a prospective, 8-week, investigator-masked, parallel-group study conducted at numerous centers in the United States, 165 previously treated patients with IOP >or= 25 mm Hg in one or both eyes after washout were randomly assigned to receive either latanoprost 0.005% once daily in the evening or unoprostone 0.15% twice daily. Observations procedures were Goldmann applanation tonometry, best-corrected visual acuity, slit lamp biomicroscopy, and ophthalmoscopy. The main outcome measure was change in the mean of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM between baseline (before treatment) and after 8 weeks of treatment.. The change in the mean +/- SD of the IOPs measured at 8:00 AM, 12 noon, and 4:00 PM was -7.2 +/- 3.2 mm Hg (28%) for latanoprost (25.3 +/- 2.8 mm Hg at baseline to 18.2 +/- 2.8 mm Hg at 8 weeks) and -3.9 +/- 2.6 mm Hg (15%) for unoprostone (25.5 +/- 3.3 mm Hg at baseline to 21.6 +/- 4.0 mm Hg; P

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Ophthalmoscopy; Prospective Studies; Prostaglandins F, Synthetic; Tonometry, Ocular; Treatment Outcome; Visual Acuity

To compare the efficacy and safety of latanoprost versus isopropyl unoprostone (unoprostone) in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).. An 8-week, multicenter, randomized, comparative study was performed in 48 Japanese patients with POAG or OH. Four patients (two in each group) withdrew from the study, but their data were included in the safety assessment but not in the intraocular pressure (IOP) evaluation. The patients were randomly treated with latanoprost 0.005% once daily or unoprostone 0.12% twice daily for 8 weeks. IOP was measured at baseline and 2, 4, and 8 weeks after treatment. In addition, ocular and systemic adverse events were recorded.. The baseline IOPs were similar between the latanoprost (n = 25) and unoprostone (n = 19) groups (24.3 +/- 2.4 mm Hg vs 23.3 +/- 2.1 mm Hg, respectively, = 0.18). The IOP reductions from baseline at 2, 4, and 8 weeks after treatment were 5.8 +/- 2.4, 6.6 +/- 2.5, and 6.7 +/- 2.0 mm Hg in the latanoprost group, and 3.8 +/- 2.0, 3.5 +/- 2.3, and 3.3 +/- 3.0 mm Hg in the unoprostone group, respectively. The IOP reduction in the latanoprost group at 8 weeks was larger than that in the unoprostone group ( < 0.001, analysis of covariance). Five adverse events were observed in 4 (15%) of 27 patients in the latanoprost group, and five adverse events were observed in 4 (20%) of 21 patients in the unoprostone group. There was no difference in the incidence of adverse events between groups ( = 0.71).. Latanoprost produced a statistically greater reduction in IOP than unoprostone in Japanese patients with POAG or OH.

Topics: Antihypertensive Agents; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Japan; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety

A long-term comparison of the ocular hypotensive efficacy and safety of unoprostone isopropyl 0.15% twice daily with that of timolol maleate 0.5% twice daily and betaxolol HCl 0.5% twice daily.. This was a randomized, multicenter, double-masked, active-controlled 24-month clinical trial involving 27 centers in Europe and Israel.. The study population was composed of patients with primary open-angle glaucoma (including pseudoexfoliation) or ocular hypertension. After washout of antiglaucoma medications, intraocular pressure (IOP) was measured at 0, + 2, + 8, and + 12 hours. Patients were randomized in a 2:1:1 ratio to unoprostone, timolol, or betaxolol. Patients returned for examinations at 2 and 6 weeks and 3 and 6 months.. 556 patients were randomized. Each drug produced a clinically and statistically (P <.001) significant reduction from baseline in 12-hour diurnal IOP at month 6 (- 4.3 mm Hg, unoprostone; - 5.8 mm Hg, timolol; - 4.9 mm Hg, betaxolol). Differences in adjusted treatment means between unoprostone and timolol and unoprostone and betaxolol were 1.57 mm Hg (95% CI: 1.00, 2.13) and 0.53 mm Hg (95% CI: - 0.03, 1.09), respectively. Unoprostone was clinically equivalent to betaxolol but did not have as great an IOP-lowering effect as timolol. Discontinued for inadequate control of IOP were 7%, 1%, and 4% of the patients for unoprostone, timolol, and betaxolol, respectively. There were no changes of note in visual acuity, pupil size, cup-to-disk ratio, visual fields, or iris color. Changes in heart rate and blood pressure were small, with no clinically significant differences between groups.. Unoprostone provided a clinically significant IOP-lowering effect equivalent to betaxolol but not to timolol. The side effect profile of unoprostone appears to be comparable to other established IOP-lowering agents.

Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Betaxolol; Dinoprost; Double-Blind Method; Exfoliation Syndrome; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pupil; Safety; Timolol; Visual Acuity; Visual Fields

To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) METHODS: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measurements was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used.. 28 patients completed both treatment periods and had IOP data available for evaluation. After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg and 24.4 (1.1) mm Hg respectively (p = 0.18). When latanoprost once daily was given to patients treated with unoprostone, there was additional IOP lowering of 1.9 (0.6) mm Hg (p = 0.012). However, adding unoprostone to those being treated with latanoprost produced an IOP change of +0.4 (0.5) mm Hg (p = 0.42). Ocular symptoms and findings were mild and equally distributed between treatment groups, and after combined therapy. Hyperaemia and ocular irritation were the most frequently reported events. Over a third of patients experienced ocular irritation with the combination of medications.. Latanoprost once daily causes additional IOP lowering in eyes which were being treated with unoprostone twice a day. However, there was no additional IOP lowering when unoprostone was added to eyes which were being treated with latanoprost. Both drugs were well tolerated together with few ocular adverse events.

Topics: Adult; Aged; Antihypertensive Agents; Dinoprost; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic

To compare the intraocular pressure (IOP) reducing effect and safety of latanoprost 0.005% once daily with unoprostone 0.12% twice daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).. An 8-week, double-masked, randomized, parallel-group, single-center clinical trial.. A total of 108 patients with POAG or OH were enrolled.. After completing a wash-out of ocular hypotensive medications, patients were randomized to receive either latanoprost once daily in the evening plus placebo once daily in the morning, or unoprostone twice daily (morning and evening).. IOP was measured at 10:00 AM and at 5:00 PM at baseline and at week 8, and before 12:00 noon at week 2. Ocular and systemic safety assessments were performed.. From an overall baseline of 24.1 mmHg, latanoprost reduced IOP by 6.7 mmHg (28%) and unoprostone reduced IOP by 3.3 mmHg (14%). The difference between the groups of 3.4 mmHg was significant (P: < 0.001, analysis of covariance; 95% confidence interval [CI]: -4.7 to -2.1) in favor of latanoprost. A >/=30% reduction in mean IOP from baseline was achieved by 44% of latanoprost-treated patients compared with 8% of unoprostone-treated patients. The incidence of adverse events was low and comparable between the groups.. Latanoprost administered once daily was significantly more effective in reducing IOP compared with unoprostone administered twice daily in patients with POAG and OH.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety; Treatment Outcome

To evaluate the safety and efficacy of adding unoprostone isopropyl 0.12% vs placebo both given twice daily to latanoprost 0.005% given every evening.. We treated 41 patients with primary open-angle glaucoma or ocular hypertension with latanoprost 0.005% for 1 month and then randomized each to either placebo or unoprostone isopropyl 0.12% for 8 weeks. Diurnal intraocular pressures were measured at 08:00, 10:00, 12:00, 18:00, and 20:00 hours, both at baseline (time of randomization) and after 8 weeks of treatment.. Twenty patients were treated in the placebo group and 21 in the unoprostone isopropyl group. After 8 weeks of treatment in the placebo group, the trough intraocular pressure at 08:00 and the diurnal pressure were 20.4 +/- 3.2 and 19.1 +/- 2.2 mm Hg, respectively. In the unoprostone isopropyl group the pressures were 19.4 +/- 3.3 and 18.0 +/- 1.7 mm Hg (P =.22 and P =.042), respectively. However, eyes with a baseline pressure of 22 mm Hg or greater on latanoprost had an average 3.3 mm Hg greater reduction at trough (P <.01) and a 2.1 mm Hg greater decrease in diurnal pressure (P =.030) after adding unoprostone isopropyl (n = 14 eyes) compared with placebo (n = 16 eyes; P <.001). In addition, the range of the pressures throughout the diurnal curve was reduced from 2.7 mm Hg on latanoprost alone to 1.4 mm Hg after adding unoprostone isopropyl. Adverse events were similar between groups, and no patients were discontinued because of safety reasons.. This study suggests that unoprostone isopropyl can safely improve the diurnal curve characteristics in patients who continue to have an elevated pressure on latanoprost 0.005% alone.

Topics: Antihypertensive Agents; Dinoprost; Double-Blind Method; Drug Synergism; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Safety; Treatment Outcome

To compare the intraocular pressure)-lowering effect and side effects of latanoprost 0.005% once daily with unoprostone 0.12% twice daily.. Sixty patients with primary open-angle glaucoma or ocular hypertension were randomized to receive either latanoprost once daily in the evening and placebo once daily in the morning, or unoprostone twice daily in the morning and evening. The study was double masked and followed a crossover design with two treatment periods of 1 month separated by a 3-week washout period. The intraocular pressure was measured at 9 AM and 5 PM on the baseline and day 28 visits, and at 9 AM on day 2 and day 14 visits of each treatment period. The 9 AM measurement was taken 2 hours and 13 hours after the last drop of unoprostone and latanoprost, and the 5 PM measurement was at 10 and 21 hours, respectively. The mean of the measurements was calculated. Safety parameters were also recorded.. Fifty-six patients completed both treatment periods and had intraocular pressure data available for evaluation. After 1 month of treatment, latanoprost significantly reduced intraocular pressure (mean +/- SEM) by 6.1 +/- 0.5 mm Hg (P <.001) and unoprostone by 4.2 +/- 0.4 mm Hg (P <.001) adjusted from an overall baseline of 22.3 +/- 0.5 mm Hg and 23.2 +/- 0.4 mm Hg, respectively. The difference of 1.9 mm Hg between treatments was statistically significant in favor of latanoprost [P =.003, analysis of covariance (ANCOVA)]. Unadjusted analysis of responders using the percentage decrease in intraocular pressure showed that the proportion of responders in the latanoprost-treated group was greater than in the unoprostone-treated group. Adverse ocular symptoms and findings were mild in both treatment groups. Eye redness and ocular irritation were the most frequently reported events.. Latanoprost once daily was significantly more effective in reducing intraocular pressure compared with unoprostone twice daily after 1 month of treatment in patients with primary open-angle glaucoma and ocular hypertension. Both drugs were well tolerated with few ocular adverse events.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Cross-Over Studies; Dinoprost; Double-Blind Method; Drug Evaluation; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Treatment Outcome

To investigate the clinical characteristics of docosanoid derivative, isopropyl unoprostone in the treatment of primary open angle glaucoma (POAG).. In 17 patients (22 eyes) with POAG we analysed prospectively the effect of Rescula upon intraocular pressure, aqueous flare, pupil size, ocular signs and symptoms. Patients were followed up every 2 weeks for at least 8 weeks with complete ocular examination. Concomitant topical therapeutics were used in the study: 0.5% Timolol--group I (16 eyes), and 0.5% Timolol + 2% Dorzolamide--group II (6 eyes).. Mean (+/- SD) pretreatment pressure was 24.7 +/- 4.3 mm Hg in group I and it was reduced by 3.7 mm Hg (13.5%) (p < 0.05) at the end of the follow up. In group I Rescula was very effective (delta T% > 25%) in 6/16 eyes (37.5%) and it was ineffective (delta T% < 10%) in the same number of eyes. In group II pretreatment pressure was 24.8 +/- 2.6 mm Hg and it was reduced by 2.6 mm Hg (10.6%) (p = 0.1). Rescula induced no elevation of the aqueous flare during the treatment. No effect on pupil size was observed, either. Eye stinging/conjunctival hyperaemia was noted in 2/17 patients and punctate epitheliopathy in 1 patient (5.9%) that caused discontinuation of drops.. Unoprostone produced significant additive effect to Timolol. Thus, it may be a valuable option for adjunctive therapy. However, interindividual differences need to be considered, as in some patients the response was insignificant.

Topics: Administration, Topical; Antihypertensive Agents; Dinoprost; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Prospective Studies; Sulfonamides; Thiophenes; Timolol

To compare the intraocular pressure-lowering effect of unoprostone isopropyl (unoprostone) 0.12% and latanoprost 0.005%. A correlation between the intraocular pressure-lowering effect of unoprostone and latanoprost was also evaluated.. A single-masked randomized study included 18 patients between 49 and 68 years (mean, 60.7 +/- 5.1 years) with an intraocular pressure of both eyes from 21 to 27 mm Hg. The patients were prospectively randomized to receive latanoprost in the right eye and unoprostone in the left eye, or unoprostone in the right eye and latanoprost in the left eye. The patients were followed up for 8 weeks. This study evaluated the intraocular pressure-lowering effect and incidence of drug-related side effects.. Mean baseline intraocular pressure was 22.8 +/- 1.2 mm Hg in latanoprost-treated eyes and 22.4 +/- 1.0 mm Hg in unoprostone-treated eyes; there was no statistically significant difference between these groups. Mean intraocular pressure at 8 weeks after the start of the administration was 16.7 +/- 2.0 mm Hg in latanoprost-treated eyes and 19.0 +/- 1.5 mm Hg in unoprostone-treated eyes. Patients in the latanoprost-treated group showed a greater intraocular pressure reduction compared with those in the unoprostone-treated group. Mean intraocular pressure changes in latanoprost-treated eyes were significantly greater at every visit (P < 0.0001). A change of intraocular pressure at 8 weeks in the latanoprost-treated eyes was significantly correlated with that in the contralateral unoprostone-treated eyes (r = 0.665, P = 0.0013) (Figure). There was no significant difference in the rate of ocular side effects between latanoprost- and unoprostone-treated eyes.. Latanoprost appears to have a more beneficial effect for intraocular pressure control compared with unoprostone. An intraocular pressure reduction in the latanoprost-treated eyes was significantly correlated with that in the contralateral unoprostone-treated eyes. There was no significant difference in the incidence of ocular side effects between both drugs. Further investigation using more cases and longer follow-up periods are needed.

Topics: Aged; Antihypertensive Agents; Dinoprost; Drug Evaluation; Female; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F, Synthetic; Safety; Single-Blind Method; Tonometry, Ocular; Treatment Outcome

Topics: Antihypertensive Agents; Dinoprost; Drug Evaluation; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; Treatment Outcome

The efficacy of 0.5% timolol was compared with that of the prostaglandin derivative unoprostone in maintaining control of intraocular pressure (IOP) in subjects with chronic open angle glaucoma (COAG) or ocular hypertension (OH) already responding satisfactorily to beta-blocker monotherapy. In a two-centre, double-masked, randomised parallel group study, 40 subjects were placed on 0.5% timolol eyedrops twice daily for two weeks. They were then randomised either to continue with 0.5% timolol or to switch to 0.12% unoprostone, applied twice daily for six weeks. IOP was measured at two-weekly intervals. The status of the conjunctiva, iris, cornea and anterior chamber was kept under observation. Ocular safety was monitored by measurements of visual acuity, and any systemic adverse events were recorded. After six weeks' treatment, there were no statistically significant differences in mean change from baseline IOP within or between treatment groups. For the subjects treated with unoprostone, mean IOP increased by 0.69 mm Hg (p = 0.368) while that of the timolol-treated subjects fell by 0.47 mm Hg (p = 0.287). The difference in mean IOP between groups was 1.16 mm Hg (p = 0.211, 95% confidence interval [CI] -0.69 to 3.02). The most common complaint was a mild and transient burning sensation on instillation which occurred more frequently in the unoprostone group. In conclusion, an aqueous solution of 0.12% unoprostone isopropyl, applied topically to the eye twice daily for six weeks, was as effective as 0.5% timolol in maintaining control of IOP in subjects with chronic open angle glaucoma or ocular hypertension. Both treatments were safe and well tolerated.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Antihypertensive Agents; Chronic Disease; Depression, Chemical; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Statistics, Nonparametric; Time Factors; Timolol

To compare the effect of unoprostone isopropyl 0.12% to that of timolol maleate 0.5% solution given twice daily on the diurnal curve of intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension.. In this investigator-masked, single-center, parallel-group comparison, 36 patients with primary open-angle glaucoma or ocular hypertension were randomized in a 2:1 ratio to receive either unoprostone isopropyl 0.12% or placebo/timolol maleate 0.5% solution, respectively. A placebo-controlled diurnal curve on day 0 and active-controlled diurnal curves at weeks 2 and 4 were performed at 0, 2, 4, 6, 8, 10, 12, and 24 hours. At week 2, administration of unoprostone isopropyl twice daily was compared with administration of timolol maleate twice daily. At week 4, administration of unoprostone isopropyl three times daily was compared with administration of timolol maleate twice daily.. At the 24-hour 8:00 AM trough at week 2, administration of unoprostone isopropyl twice daily decreased IOP from 23.4 +/- 2.0 mmHg at baseline to 19.3 +/- 4.4 mmHg, and timolol maleate reduced IOP from 24.4 +/- 2.6 mmHg to 17.5 +/- 2.9 mmHg. At the 8:00 AM trough at week 4, unoprostone isopropyl given three times daily produced an IOP of 19.6 +/- 3.3 mmHg and timolol maleate resulted in an IOP of 19.4 +/- 3.0 mmHg. No statistical differences between groups were observed at any time point during either diurnal curve. Safety was similar in the two treatment groups, with no differences between groups in conjunctival hyperemia, anterior segment inflammation, or iris color change.. Results of this short-term pilot trial indicate that unoprostone isopropyl may be safe and effective in reducing IOP from baseline when given twice or three times daily.

Topics: Circadian Rhythm; Dinoprost; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Safety; Timolol; Visual Acuity

We have reviewed two Phase III clinical studies of isopropyl unoprostone conducted in Japan: a 12-week comparative study of 0.12% isopropyl unoprostone and 0.5% timolol, and a 52-week administration of two concentrations of isopropyl unoprostone in ocular hypertensive and primary open-angle glaucoma patients. These studies showed a similar ocular hypotensive effect of 0.12% isopropyl unoprostone to 0.5% timolol and a sustained ocular hypotensive effect of the drug for up to one year. Adverse reactions of isopropyl unoprostone were minor and similar to those of timolol. No pigmentary changes of the irides were noticed. In view of these results, isopropyl unoprostone seems to be a useful antiglaucoma medication.

Topics: Administration, Topical; Adrenergic beta-Antagonists; Animals; Dinoprost; Drug Evaluation; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Timolol; Treatment Outcome

A double-masked comparative clinical study of UF-021 (Rescula), a unique prostaglandin-related compound, was carried out at 18 centers with timolol maleate 0.5% ophthalmic solution as an active reference drug. After a wash-out period, UF-021 (0.12%) or timolol (0.5%) was given topically twice a day for 12 weeks to 158 patients with primary open-angle glaucoma or ocular hypertension, in a randomized double-masked manner. Both groups showed a significant reduction in intraocular pressure from the second week to the end of the study. In overall improvement rating, 91.4% of the cases (64/70) in the UF-021 group and 88.3% (68/77) in the timolol group were judged to be "Extremely improved" or "Improved". Five and 4 cases reported having side effects in the UF-021 and timolol groups, respectively, but none of the cases required any change or discontinuation of treatment. While UF-021 did not affect blood pressure, both systolic and diastolic blood pressures in the timolol group were significantly decreased. These results suggest that UF-021 (0.12%) has the potential to lower intraocular pressure equivalent to timolol (0.5%), while having no effect on cardiovascular functions.

Topics: Administration, Topical; Blood Pressure; Dinoprost; Double-Blind Method; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Timolol

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

Topics: Aqueous Humor; Biological Transport, Active; Cell Membrane Permeability; Dinoprost; Double-Blind Method; Drug Tolerance; Fluorophotometry; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; 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

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

Glaucoma is a neurodegenerative disease that leads to blindness, and lowering intraocular pressure (IOP) is very important in glaucoma treatment. The trabecular meshwork is responsible for aqueous humor outflow, and the accumulation of fibronectin in trabecular meshwork is known to cause ocular hypertension. We have already shown that Piezo1 activation has an IOP lowering effect in mice and suppresses fibronectin expression level in human trabecular meshwork cells (HTMC). In this study, we report the mechanism of the reduction of fibronectin caused by Piezo1 activation. Activation of Piezo1 in HTMC showed increased expression of matrix metalloproteinase-2 (MMP-2) and cyclooxygenase (COX)-2, and decreased fibronectin expression. In addition, Piezo1 activation enhanced phosphorylation of cytosolic phospholipase A2 (cPLA2), and inhibitors targeting cPLA2 and COX-2 suppressed Yoda 1, a Piezo1 agonist, induced fibronectin reduction. These results indicate that the arachidonic acid cascade underlies this reaction, and, in support of this hypothesis, activation of Piezo1 promoted secretion of prostaglandin F2α (PGF2α) in HTMC. These results indicate that the activation of Piezo1 in HTMC promotes the degrading of fibronectin by promoting the arachidonic acid cascade and increasing the expression of PGF2α and MMP-2.

Topics: Animals; Aqueous Humor; Arachidonic Acid; Dinoprost; Fibronectins; Glaucoma; Intraocular Pressure; Ion Channels; Matrix Metalloproteinase 2; Mice; Neurodegenerative Diseases; Ocular Hypertension; Phospholipases A2, Cytosolic; Trabecular Meshwork

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.

Topics: Antihypertensive Agents; Chemistry Techniques, Synthetic; Dinoprost; Glaucoma; Molecular Structure; Ocular Hypertension; Prostaglandins F

We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs.. This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire.. There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001).. The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Eyelashes; Eyelid Diseases; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Skin Pigmentation; Surveys and Questionnaires; Travoprost

The IOP lowering effects of NCX 139, a new chemical entity comprising latanoprost amide and a NO-donating moiety, were compared to those of the respective des-nitro analog in in vitro assays and in rabbit and dog models of ocular hypertension. The NO donor, molsidomine as well as the prostamide bimatoprost (Lumigan(®)) and the prostaglandin agonist, latanoprost (Xalatan(®)) were also investigated for comparison. NCX 139 but not its des-nitro analog resulted in NO-mediated vascular relaxant effect in pre-contracted rabbit aortic rings (EC(50)=0.70±0.06 μM; E(max)=80.6±2.9%). Like bimatoprost (IC(50)=3.07±1.3 μM) or latanoprost (IC(50)=0.48±0.15 μM), NCX 139 displaced (3)H-PGF2α binding on recombinant human prostaglandin-F (FP) receptors with an estimated potency of 0.77±0.13 μM. In transient ocular hypertensive rabbits, bimatoprost and latanoprost were not effective while molsidomine elicited a dose-dependent reduction of IOP confirming the responsiveness of rabbits to NO but not to FP receptor agonists. NCX 139 tested at a therapeutically relevant dose, significantly lowered IOP while the des-nitro analog was not effective (0.03% NCX 139, Δ(max)=-12.8±2.0 mmHg). In glaucomatous dogs, 0.03% NCX 139 decreased IOP to a greater extent compared to an equimolar dose of the respective des-nitro derivative (Δ(max)=-4.6±1.0 and -2.7±1.3 mmHg, respectively for NCX 139 and its des-nitro analog). Albeit with low potency, NCX 139 also resulted effective in normotensive dogs while it did not reduce IOP in normotensive rabbits. NCX 139, a compound targeting two different and important mechanisms, is endowed with ocular hypotensive effects more evident in hypertensive conditions which may be of interest in the search of more effective treatments for hypertensive glaucoma.

Topics: Amides; Animals; Antihypertensive Agents; Aorta; Bimatoprost; Chromatography, High Pressure Liquid; Cloprostenol; Dinoprost; Disease Models, Animal; Dogs; Glaucoma; Intraocular Pressure; Latanoprost; Male; Molsidomine; Nitrates; Nitric Oxide; Nitric Oxide Donors; Ocular Hypertension; Prostaglandins F, Synthetic; Rabbits; Tandem Mass Spectrometry; Tonometry, Ocular; Vasodilation; Vasodilator Agents

The aim of the study was to investigate the ocular hypotensive activity of a nitric oxide (NO)-donating latanoprost, BOL-303259-X, following topical administration. The effect of BOL-303259-X (also known as NCX 116 and PF-3187207) on intraocular pressure (IOP) was investigated in monkeys with laser-induced ocular hypertension, dogs with naturally-occurring glaucoma and rabbits with saline-induced ocular hypertension. Latanoprost was used as reference drug. NO, downstream effector cGMP, and latanoprost acid were determined in ocular tissues following BOL-303259-X administration as an index of prostaglandin and NO-mediated activities. In primates, a maximum decrease in IOP of 31% and 35% relative to baseline was achieved with BOL-303259-X at doses of 0.036% (9 μg) and 0.12% (36 μg), respectively. In comparison, latanoprost elicited a greater response than vehicle only at 0.1% (30 μg) with a peak effect of 26%. In glaucomatous dogs, IOP decreased from baseline by 44% and 10% following BOL-303259-X (0.036%) and vehicle, respectively. Latanoprost (0.030%) lowered IOP by 27% and vehicle by 9%. Intravitreal injection of hypertonic saline in rabbits increased IOP transiently. Latanoprost did not modulate this response, whereas BOL-303259-X (0.036%) significantly blunted the hypertensive phase. Following BOL-303259-X treatment, latanoprost acid was significantly elevated in rabbit and primate cornea, iris/ciliary body and aqueous humor as was cGMP in aqueous humor. BOL-303259-X lowered IOP more effectively than latanoprost presumably as a consequence of a contribution by NO in addition to its prostaglandin activity. The compound is now in clinical development for the treatment of glaucoma and ocular hypertension.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Aqueous Humor; Cell Line; Ciliary Body; Cyclic GMP; Dinoprost; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Female; Glaucoma; Guanylate Cyclase; Intraocular Pressure; Iris; Latanoprost; Macaca fascicularis; Male; Nitric Oxide; Nitric Oxide Donors; Ocular Hypertension; Prostaglandins F, Synthetic; Rabbits; Rats; Tonometry, Ocular

This study compared the toxicity profiles of three antiglaucoma prostaglandin F2alpha analogs, latanoprost, travoprost, and bimatoprost which contain benzalkonium chloride (BAK), with tafluprost, a new preservative-free prostaglandin analog.. IOBA-NHC cells were exposed to BAK-containing prostanoid solutions, their respective BAK concentrations, and preservative-free tafluprost solution for 30 min. Membrane integrity, apoptosis, oxidative stress, and cells morphology were evaluated.. Preservative-free tafluprost resulted in significantly higher membrane integrity and lower pro-apoptotic and pro-oxidative effects than preservative-containing prostaglandin analog preparations.. These results suggest that tafluprost, a new preservative-free prostaglandin analog, has very low or no pro-apoptotic, pro-necrotic, or pro-oxidative effects in vitro compared to preservative-containing formulations.

Topics: Amides; Apoptosis; Benzalkonium Compounds; Bimatoprost; Cell Line; Cell Membrane; Cell Survival; Cloprostenol; Conjunctiva; Dinoprost; DNA; Drug Combinations; Epithelial Cells; Glaucoma; Humans; Latanoprost; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Superoxides; Travoprost

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Dinoprost; Drug Interactions; Humans; Ocular Hypertension; Prostaglandins, Synthetic

The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically. Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension. In clinical studies, AL-6598 0.01% provided a sustained intraocular pressure reduction with q.d. application; b.i.d. provided greater intraocular pressure control. The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine.

Topics: Animals; Antihypertensive Agents; Aqueous Humor; Cats; Cloprostenol; Dinoprost; Dose-Response Relationship, Drug; Female; Glaucoma, Open-Angle; Guinea Pigs; Humans; Intraocular Pressure; Macaca fascicularis; Male; Ocular Hypertension; Rabbits; Randomized Controlled Trials as Topic; Receptors, Immunologic; Receptors, Prostaglandin; Safety; Structure-Activity Relationship; Timolol; Travoprost

Topics: 3T3 Cells; Animals; Antihypertensive Agents; Calcium Signaling; Cats; Dinoprost; Iris; Mice; Muscle, Smooth; Ocular Hypertension

Topics: Antihypertensive Agents; Data Interpretation, Statistical; Dinoprost; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic

Topics: Antihypertensive Agents; Data Interpretation, Statistical; Dinoprost; Drug Synergism; Drug Therapy, Combination; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic

Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.

Topics: Adenylyl Cyclases; Administration, Topical; Animals; Antihypertensive Agents; Cats; Cattle; Cloprostenol; Corpus Luteum; Dinoprost; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Fibroblasts; Humans; Intraocular Pressure; Macaca; Mice; Ocular Hypertension; Ophthalmic Solutions; Phosphatidylinositols; Rabbits; Receptors, Prostaglandin; Trabecular Meshwork; Travoprost

Topics: Administration, Topical; Adult; Ciliary Body; Corneal Edema; Dinoprost; Female; Glaucoma; Humans; Intraocular Pressure; Laser Therapy; Latanoprost; Ocular Hypertension; Prostaglandins F, Synthetic; Retinitis Pigmentosa

It has been shown that prostaglandin A2 (PGA2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA2-1-isopropyl ester (PGA2-IE) than with PGA2, PGF2 alpha-1-isopropyl ester (PGF2 alpha-IE), or any other known ocular hypotensive agent. Furthermore, single applications of 0.5 microgram of PGA2-IE maintain significant IOP reductions for at least 24 hr. This hypotensive effect is enhanced during the first 3-5 days of daily treatment. Significant IOP reductions were maintained for several months as long as PGA2-IE was applied daily or at least once every 48 hr. None of the cats manifested signs of discomfort in response to treatment with doses ranging from 0.10 to 1.25 micrograms of PGA2-IE. Moreover, the extent of anterior chamber flare was less than that typically observed after the topical application of hypotensive doses of PGE2, PGD2, PGF2 alpha, or the esters or tromethamine salt of PGF2 alpha. Although it is possible that the human eye would respond differently to PGs of the A type, the results of these studies suggests that PGA2-IE or other esters of derived PGs of the A type, and probably the B type, may offer significant therapeutic advantages over the PGF2 alpha tromethamine salt and PGF2 alpha-IE, which have been shown to exert significant hypotensive effects on normal and glaucomatous human eyes.

Topics: Administration, Topical; Animals; Cats; Dinoprost; Dose-Response Relationship, Drug; Female; Intraocular Pressure; Male; Ocular Hypertension; Prostaglandins A; Prostaglandins A, Synthetic; Prostaglandins F, Synthetic; Time Factors