Boyle J E, Ghosh K, Gieser D K, Adamsons I A
Department of Clinical Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Ophthalmology. 1999 Dec;106(12 Suppl):10-6.
To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications.
A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial.
A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated.
After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily.
Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit.
Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye.
After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.
比较2.0%多佐胺和0.5%噻吗洛尔固定复方制剂每日给药两次与各单一组分按常规单药治疗剂量方案给药，在停用所有降眼压药物的患者中的疗效和安全性。
一项为期3个月的平行、随机、双盲、活性药物对照、多中心临床试验。
共有335例双侧高眼压或开角型青光眼患者参与。
在完成降眼压药物洗脱期后，患者被随机分为接受多佐胺-噻吗洛尔复方制剂每日两次加安慰剂每日一次、0.5%噻吗洛尔每日两次加安慰剂每日一次或2.0%多佐胺每日三次。
在第1天、第2周以及第1、2和3个月，于早晨低谷期（0小时）和高峰期（给药后2小时）测量眼压。每次研究访视时评估眼部和全身安全性。
复方制剂组眼压降低幅度平均大于多佐胺组和噻吗洛尔组。在早晨低谷期（第3个月，0小时），复方制剂组眼压较基线平均降低27.4%（-7.7 mmHg），多佐胺组为15.5%（-4.6 mmHg），噻吗洛尔组为22.2%（-6.4 mmHg）。在早晨高峰期（第3个月，2小时），复方制剂组、多佐胺组和噻吗洛尔组眼压较基线平均降低幅度分别为32.7%（-9.0 mmHg）、19.8%（-5.4 mmHg）和22.6%（-6.3 mmHg）。总体而言，复方制剂与其各单一组分临床不良事件的发生率相当。因临床不良事件而退出研究的患者比例在复方制剂组和多佐胺组之间也相当，尽管复方制剂组显著高于噻吗洛尔组（7%对1%，P = 0.035）。同样，复方制剂组和多佐胺组报告眼部症状的患者数量相当；然而，与噻吗洛尔组相比，接受复方制剂治疗的患者中更多人报告有视力模糊、眼烧灼感、眼刺痛和流泪。
在停用降眼压治疗后，多佐胺-噻吗洛尔复方制剂降低眼压的效果优于其任何一种单一组分作为单药治疗的效果。该复方制剂总体耐受性良好，为联合使用其单一组分提供了一种方便的替代方案。
