Effect of different dose schedules of latanoprost on intraocular pressure and pupil size in the glaucomatous Beagle.

Abstract

To evaluate the changes in intraocular pressure and pupil size in glaucomatous dogs after instillation of 0.005% latanoprost (Xalatan, Pharmacia and Upjohn, Kalamazoo, MI, USA) once in the morning, or once in the evening, or twice daily in five-day multiple-dose studies. Animals studied Eight Beagles with the moderate stage of inherited primary open-angle glaucoma. Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 am, 10 am, 12 noon, 2 pm, and 4 pm in eight glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.005% latanoprost was instilled in the opposite drug eye. Control and drug eyes were selected using a random table. For these three studies, 0.5% methylcellulose and 0.005% latanoprost 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). Statistical comparisons between drug groups included control, placebo, and treated (0.005% latanoprost) eyes for three multiple-dose studies. In the 8-am latanoprost study, the mean +/- SEM diurnal declines in IOP for the placebo and drug eyes for the first day were 6.5 +/- 3.6 mmHg and 8.4 +/- 4.0 mmHg, respectively. The mean +/- SEM diurnal changes in IOP after 0.005% latanoprost at 8 am once daily for the next four days were 23.3 +/- 5.0 mmHg, 25.4 +/- 2.1 mmHg, 25.7 +/- 1.7 mmHg, and 26.1 +/- 1.7 mmHg, respectively, and were significantly different from the control eye. A significant miosis also occurred starting 2 h postdrug instillation, and the resultant mean +/- SD pupil size was 1.0 +/- 0.1 mm. In the first day of the second latanoprost study, the mean +/- SEM diurnal changes in the placebo and drug eye IOPs were 11.6 +/- 3.8 mmHg, and 12.0 +/- 4.4 mmHg, respectively. For the following four days with latanoprost instilled at 8 pm, the mean +/- SEM diurnal changes in IOP in the drug eyes were 24.9 +/- 2.1 mmHg, 22.4 +/- 1.8 mmHg, 21.6 +/- 1.9 mmHg, and 26.6 +/- 2.2 mmHg, respectively. Compared to the fellow placebo eyes, the diurnal changes in IOP were significantly different. Significant changes in pupil size were similar to the IOP changes, with miosis throughout the day and return to baseline pupil size the following morning before drug instillation. In the last study, the mean +/- SEM diurnal changes in IOP for the placebo and drug eyes for the first day were 6.6 +/- 2.1 mmHg and 9.4 +/- 2.8 mmHg, respectively. For the four subsequent days with latanoprost instilled twice daily, the mean +/- SEM diurnal IOP changes were 19.6 +/- 1.5 mmHg, 19.1 +/- 1.4 mmHg, 19.9 +/- 1.7 mmHg, and 20.3 +/- 0.7 mmHg, respectively, and were significantly different from the placebo eyes. The mean changes in PS were 3.1 +/- 0.7 mm. 0.005% latanoprost instilled once daily (am or pm) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle. The evening instillation of 0.005% latanoprost produced less daily fluctuations in IOP than when the drug was instilled in the morning. 0.005% latanoprost instilled twice daily produced the greatest decline in IOP with the least daily fluctuations, but longer duration miosis.