Bartlett Jimmy D, Niemann Katherine, Houde Barbara, Allred Troy, Edmondson Marcia J, Crockett R S
School of Optometry, University of Alabama at Birmingham, 35294, USA.
J Ocul Pharmacol Ther. 2003 Jun;19(3):271-9. doi: 10.1089/108076803321908392.
The objective of this study was to determine the safety and tolerability of pirenzepine ophthalmic gel (PIR) and the magnitude of mydriatic and accommodative effects in myopic children.
This was a placebo-controlled, parallel double-masked study of unequal (4:1) randomization. Children were randomized to receive 0.5% PIR, b.i.d., or vehicle (placebo) for one week, then titrated to 1% PIR for one week, then 2% PIR for two weeks, and then for an additional 11 months. Enrolled were 26 normal healthy children, 9-12 years old, with myopia (-0.75 to -3 D) and minimal astigmatism (< or =1 D, O.U.).
Three of the 26 subjects (all in PIR group) did not complete one year of the study: one child at day 8 who inadvertently received 2.0% PIR as the first concentration, due to accommodative insufficiency, one child for follicular conjunctivitis at 9 months, and one child for administrative reasons at month 1. Other than the child discontinued at day 8, all patients were titrated up to the highest concentration of PIR evaluated. When measured 1 hour after instillation of PIR 0.5%, there was a mean mydriatic effect of less than 1 mm compared to vehicle in either bright or dim light. With increasing concentrations of PIR, this effect became numerically larger, although still remained less than 1 mm in either bright or dim light. Measured approximately 12 hours after instillation, there was little mydriasis within each group (relative to baseline) or between treatments. Similar mild PIR effects were seen on accommodative amplitude. In general, the adverse events reported were mild or moderate in severity, resolved rapidly, and were of the nature and incidence to be expected in a study of a topical anti-muscarinic gel in children of this age.
The promising efficacy results and acceptable safety profile justifies proceeding with additional clinical trials to evaluate efficacy and further characterize the safety of pirenzepine in a larger patient population.
本研究的目的是确定哌仑西平眼用凝胶（PIR）在近视儿童中的安全性和耐受性，以及散瞳和调节作用的程度。
这是一项安慰剂对照、平行双盲的不等比例（4:1）随机研究。儿童被随机分为接受0.5% PIR，每日两次，或赋形剂（安慰剂），为期一周，然后滴定至1% PIR，为期一周，再滴定至2% PIR，为期两周，然后再持续11个月。纳入了26名9至12岁的正常健康儿童，近视度数为-0.75至-3 D，散光最小（双眼均≤1 D）。
26名受试者中有3名（均在PIR组）未完成一年的研究：1名儿童在第8天因调节不足意外接受了2.0% PIR作为初始浓度，1名儿童在9个月时因滤泡性结膜炎退出，1名儿童在第1个月因管理原因退出。除了在第8天停药的儿童外，所有患者均滴定至评估的PIR最高浓度。在滴入0.5% PIR后1小时测量，与赋形剂相比，无论在明亮或昏暗光线下，平均散瞳效果均小于1 mm。随着PIR浓度的增加，这种效果在数值上变得更大，尽管在明亮或昏暗光线下仍小于1 mm。在滴入后约12小时测量，每组内（相对于基线）或治疗组之间几乎没有散瞳现象。在调节幅度上也观察到类似的轻微PIR效应。总体而言，报告的不良事件严重程度为轻度或中度，迅速缓解，其性质和发生率与该年龄儿童局部抗毒蕈碱凝胶研究中预期的一致。
有前景的疗效结果和可接受的安全性表明有理由进行额外的临床试验，以评估哌仑西平在更大患者群体中的疗效并进一步明确其安全性。
