Clineschmidt C M, Williams R D, Snyder E, Adamsons I A
Department of Clinical Research, Merck Research Laboratories, West Point, PA 19486, USA.
Ophthalmology. 1998 Oct;105(10):1952-9. doi: 10.1016/s0161-6420(98)91047-8.
To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone.
Parallel, randomized, double-masked, and active-controlled study.
Enrolled were 253 patients from 22 sites throughout the United States.
After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months.
Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component.
The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported.
The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.
在仅每日两次使用噻吗洛尔眼压（IOP）仍未得到控制的患者中，比较每日两次使用的多佐胺-噻吗洛尔固定复方制剂与其单一成分（马来酸噻吗洛尔和盐酸多佐胺）按常规单一疗法给药的效果。
平行、随机、双盲、活性对照研究。
从美国各地22个地点招募了253名患者。
在每日两次使用噻吗洛尔（噻吗心安；默克公司，新泽西州怀特豪斯站）进行3周导入期后，符合条件的患者接受以下治疗之一，为期3个月：每日两次使用复方制剂（Cosopt；默克公司，新泽西州怀特豪斯站）（加用安慰剂以确保盲法）、每日两次使用噻吗洛尔（加用安慰剂以确保盲法）或每日三次使用多佐胺（Trusopt；默克公司，新泽西州怀特豪斯站）。
比较每个治疗组内以及复方制剂组与各单一成分组之间，在第2周以及第1、2和3个月的第0小时（谷值）和第2小时（峰值）测得的眼压与基线眼压。将复方制剂的安全性与各单一成分进行比较。
在所有研究时间点，复方制剂在数值上均更优，除了第2个月、噻吗洛尔第0小时以及第2个月、多佐胺第2小时外，在所有时间点在统计学上也更优。复方制剂的安全性反映了其两种成分的安全性。报告眼部或局部不良事件的患者数量，复方制剂组（45%）和多佐胺组（45%）多于噻吗洛尔组（27%），最常报告的是眼烧灼感和/或刺痛感。
与单一成分相比，多佐胺-噻吗洛尔复方制剂能进一步降低眼压，且总体耐受性良好。
