Wilkerson M, Cyrlin M, Lippa E A, Esposito D, Deasy D, Panebianco D, Fazio R, Yablonski M, Shields M B
Department of Ophthalmology, Duke University, Durham, NC.
Arch Ophthalmol. 1993 Oct;111(10):1343-50. doi: 10.1001/archopht.1993.01090100051026.
To investigate the activity and local and systemic safety of the topical carbonic anhydrase inhibitor, dorzolamide hydrochloride.
Four-week, double-masked, randomized, placebo-controlled, parallel, three-center study.
Referral centers.
Forty-eight patients with bilateral open angle glaucoma or ocular hypertension and intraocular pressure (IOP) greater than 22 mm Hg entered the study. Two of 28 patients receiving dorzolamide and two of 20 patients receiving placebo were withdrawn due to adverse experiences.
Dorzolamide (2%) or placebo to each eye three times daily for 4 weeks.
Diurnal IOP curves; ophthalmologic evaluations including corneal ultrasound pachymetry and endothelial cell count; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug and carbonic anhydrase activity levels in red blood cells.
Mean IOP at morning trough (8 AM) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with dorzolamide (-13.3%) compared with a decrease from 27.1 mm Hg to 26.4 mm Hg with placebo (-2.3%). Peak activity occurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with dorzolamide (-18.4%) vs 26.1 mm Hg to 25.5 (-2.4%) with placebo. Mean corneal thickness was slightly increased for the dorzolamide-treated group compared with the placebo-treated group (0.009 mm vs 0.001 mm, respectively, P < .05) and changes in endothelial cell counts were similar (-24 cells/mm2 vs -27 cells/mm2, respectively, P > .25). Mean carbonic anhydrase isoenzyme II activity in red blood cells decreased to 21% of baseline in dorzolamide-treated patients. There were no clinically significant differences in ocular or laboratory parameters between the dorzolamide and placebo groups.
Dorzolamide demonstrated significant IOP lowering activity over 4 weeks. It was well tolerated and there were no clinically significant changes in ocular or systemic safety parameters.
研究局部用碳酸酐酶抑制剂盐酸多佐胺的活性以及局部和全身安全性。
为期四周的双盲、随机、安慰剂对照、平行、三中心研究。
转诊中心。
48例双侧开角型青光眼或高眼压症且眼压（IOP）大于22 mmHg的患者进入研究。接受多佐胺治疗的28例患者中有2例以及接受安慰剂治疗的20例患者中有2例因不良事件退出研究。
多佐胺（2%）或安慰剂，每只眼每日三次，共4周。
昼夜眼压曲线；眼科评估，包括角膜超声测厚和内皮细胞计数；全身评估，包括生命体征、血液化学指标、全血细胞计数、尿液分析、心电图以及红细胞中的药物和碳酸酐酶活性水平。
多佐胺治疗组晨低谷（上午8点）时的平均眼压从基线时的27.1 mmHg降至第29天的23.5 mmHg（-13.3%），而安慰剂组从27.1 mmHg降至26.4 mmHg（-2.3%）。给药后2小时出现最大活性，多佐胺治疗组眼压从基线时的26.8 mmHg降至第29天的21.8 mmHg（-18.4%），安慰剂组从26.1 mmHg降至25.5 mmHg（-2.4%）。与安慰剂治疗组相比，多佐胺治疗组的平均角膜厚度略有增加（分别为0.009 mm和0.001 mm，P <.05），内皮细胞计数变化相似（分别为-24个细胞/mm²和-27个细胞/mm²，P >.25）。多佐胺治疗患者红细胞中的平均碳酸酐酶同工酶II活性降至基线的21%。多佐胺组和安慰剂组在眼部或实验室参数方面无临床显著差异。
多佐胺在4周内显示出显著的降低眼压活性。耐受性良好，眼部或全身安全性参数无临床显著变化。
