Effect of different dose schedules of bimatoprost on intraocular pressure and pupil size in the glaucomatous Beagle.
ABSTRACT The changes in intraocular pressure and pupil size in glaucomatous dogs were evaluated after instillations of 0.03% bimatoprost (Lumigan, Allergan, Irvine, CA USA) once in the morning, or once in the evening, or twice daily in five day multiple dose studies. Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 am, 10 am, 12 noon, 2 pm, and 4 pm in 8 glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.03% bimatoprost was instilled in the opposite drug eye. Methylcellulose (0.5%) and 0.03% bimatoprost were instilled the second through the fifth days with instillations in the morning (8:30 am), or evening (8 pm), or twice daily (8:30 am and 8 pm). The mean +/- SEM diurnal changes in IOP from baseline values after 0.03% bimatoprost at 8 am once daily for the next four days were 25.0 +/- 3.2 mm Hg, 25.6 +/- 2.9 mm Hg, 25.5 +/- 3.0 mm Hg, and 26.0 +/- 3.2 mm Hg respectively, and were significantly different from the control eye. After bimatoprost was instilled at 8 pm, the mean +/- SEM changes in IOP from baseline values in the drug eyes were 27.3 +/- 2.4 mm Hg, 26.6 +/- 2.2 mm Hg, 27.2 +/- 2.5 mm Hg, and 27.3 +/- 2.6 mm Hg respectively. When 0.03% bimatoprost was instilled twice daily, the mean +/- SEM changes in IOP from baseline values were 39.1 +/- 2.3 mm Hg, 39.9 +/- 2.2 mm Hg, 39.9 +/- 2.3 mm Hg, and 39.6 +/- 2.1 mm Hg respectively, and were significantly different from the control eyes. Miosis of varying duration was frequent during the three studies. Bimatoprost instilled once daily (am or pm) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle.
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ABSTRACT: 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.Ophthalmology 02/2001; 108(2):259-63. · 5.56 Impact Factor
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ABSTRACT: To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease. Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.Investigative Ophthalmology & Visual Science 09/2000; 41(9):2566-73. · 3.44 Impact Factor
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ABSTRACT: Substantial evidence indicates that a single topical application of prostaglandins (PGs) can reduce intraocular pressure (IOP) in the eyes of several species. However, earlier literature, dealing with ocular hypertensive and inflammatory responses, shows the development of tachyphylaxis to subsequent doses of PGs. If similar tolerance developed to the ocular hypotensive effects of PGs, it would preclude the use of these agents in the treatment of chronic glaucoma. The present study shows, however, that although tachyphylaxis to the ocular hypotensive effects of PGs develops in rabbits, this is not a typical response among mammals. Significant IOP reduction was maintained in cats for up to 9 months by topical application of PGE2 at 12-, 24-, or 48-hr intervals. The IOP reduction was jeopardized seriously only when the PG was applied every other day for several days or when, on a few occasions, 3 days were allowed to elapse between PGE2 applications. Ocular hypotension was also maintained during the course of topical treatment of rhesus monkey eyes with PGF2 alpha. Short periods of pupillary constriction followed the application of each dose of PGF2 alpha to cat eyes, but the miotic response of rhesus monkeys to PGF2 alpha and cats to PGF2 was negligible. Other apparent side effects were noted, but none of these were severe or progressive. These results clearly demonstrate that tachyphylaxis, or tolerance, is not expected to present an obstacle to the development of eicosanoids and/or their derivatives as therapeutic agents for the long-term treatment of ocular hypertension and chronic glaucoma.Investigative Ophthalmology & Visual Science 04/1983; 24(3):312-9. · 3.44 Impact Factor