Effect of different dose schedules of latanoprost on intraocular pressure and pupil size in the glaucomatous Beagle
Effect of different dose schedules of latanoprost on intraocular pressure and pupil size in the glaucomatous Beagle
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DOI：
10.1046/j.1463-5216.2001.00201.x
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发表时间：
2001-01-01
影响因子：
1.6
通讯作者：
MacKay, EO
中科院分区：
文献类型：
--
作者：
Gelatt, KN;MacKay, EO
目的观察0.005%拉坦前列素对青光眼犬眼压及瞳孔大小的影响（Xalatan，Pharmacia and Upjohn，Kalamazoo，MI，USA）早晨一次，或晚上一次，在为期5天的多次给药研究中，每天两次。动物研究了8只患有中度遗传性原发性开角型青光眼的比格犬。程序压平眼压计（IOP）和瞳孔大小（在8只青光眼狗中，在上午8点、上午10点、中午12点、下午2点和下午4点获得测量值。将甲基纤维素（0.5%作为安慰剂）滴入对照眼，将0.005%拉坦前列素滴入对侧药物眼。使用随机表选择对照眼和药物眼。对于这三项研究，在第二天至第五天滴注0.5%甲基纤维素和0.005%拉坦前列素，在早晨（8.30 am）或晚上（8 pm）滴注，或每日两次（8.30 am和8 pm）滴注。药物组之间的统计学比较包括对照组、安慰剂组和治疗组（0.005%拉坦前列素）眼，用于3个多次给药研究。结果在上午8点的拉坦前列素研究中，第一天安慰剂组和药物组眼的平均眼压昼夜下降值分别为6.5 +/- 3.6 mmHg和8.4 +/- 4.0 mmHg。0.005%拉坦前列素在上午8点每日一次给药后4天的平均SEM IOP昼夜变化分别为2.3 +/- 5.0 mmHg、25.4 +/- 2.1 mmHg、25.7 +/- 1.7 mmHg和26.1 +/- 1.7 mmHg，与对照眼显著不同。在药物滴注后2小时开始也出现了显著的瞳孔缩小，由此产生的平均SID瞳孔大小为1.0 +/- 0.1 mm。在第二项拉坦前列素研究的第一天，安慰剂和药物眼IOP的平均+/- SEM昼夜变化分别为11.6 +/- 3.8 mmHg和12.0 +/- 4.4 mmHg。在随后的4天中，在晚上8点滴注拉坦前列素，用药眼IOP的平均+/- SEM昼夜变化分别为24.9 +/- 2.1 mmHg、22.4 +/- 1.8 mmHg、21.6 +/- 1.9 mmHg和26.6 +/- 2.2 mmHg。与对侧安慰剂眼相比，IOP的昼夜变化显著不同。瞳孔大小的显着变化与IOP变化有关，全天瞳孔缩小，并在早上滴注药物前恢复到基线瞳孔大小。在最后一项研究中，第一天安慰剂和药物眼的IOP平均SEM昼夜变化分别为6.6 +/- 2.1 mmHg和9.4 +/- 2.8 mmHg。在随后的4天内，每天两次滴注拉坦前列素，平均+/- SEM昼夜IOP变化分别为19.6 +/- 1.5 mmHg、19.1 +/- 1.4 mmHg、19.9 +/- 1.7 mmHg和20.3 +/- 0.7 mmHg，与安慰剂眼显著不同。PS的平均变化为3.1 ± 0.7 mm。结论0.005%拉坦前列素每日一次（上午或下午）和每日两次滴注可显著降低青光眼Beagle犬的IOP和PS。晚上滴注0.005%拉坦前列素产生的IOP每日波动小于早晨滴注药物时。每天两次滴注0.005%拉坦前列素可使IOP下降最大，每日波动最小，但瞳孔缩小持续时间较长。
Objective 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.Procedures 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.Results 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 2.3 +/- 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 SID 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 to the IOP changes, with miosis throughout the day and return to baseline pupil size 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.Conclusion 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.