钙通道阻滞剂氟桂利嗪对猴眼压及房水动力学的影响。

Effect of flunarizine, a calcium channel blocker, on intraocular pressure and aqueous humor dynamics in monkeys.

作者信息

Wang Rong-Fang, Gagliuso Donna J, Podos Steven M

机构信息

Department of Ophthalmology, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA.

出版信息

J Glaucoma. 2008 Jan-Feb;17(1):73-8. doi: 10.1097/IJG.0b013e318133a845.

DOI:10.1097/IJG.0b013e318133a845

PMID:18303390

Abstract

PURPOSE

To evaluate the effects of flunarizine, a nonselective calcium channel blocker, on intraocular pressure (IOP) in monkeys with laser-induced unilateral glaucoma and on aqueous humor dynamics in normal monkeys.

METHODS

The IOP was measured before and hourly for 6 hours after single-dose administration of 0.5%, 1%, or 2% flunarizine to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. In a separate multiple-dose study, 0.5% flunarizine was applied twice daily for 5 consecutive days to the glaucomatous eye of the same 8 monkeys. IOP was measured at untreated baseline, after treatment with vehicle only, and on treatment days 1, 3, and 5. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 7 normal monkeys before and after the fifth dose of twice-daily treatment with 0.5% flunarizine.

RESULTS

Unilateral application of 50 microL of 0.5%, 1%, or 2% flunarizine reduced IOP bilaterally. In the treated glaucomatous eyes, flunarizine reduced the IOP for 2, 3, or 5 hours, with a maximum reduction of 2.5+/-0.5 (mean+/-SEM) mm Hg (9%), 3.0+/-0.4 mm Hg (10%), and 5.0+/-0.8 mm Hg (18%) following the 0.5%, 1%, and 2% concentrations, respectively (P<0.01). The maximum reductions in IOP in the contralateral untreated eyes were 1.3+/-0.5 mm Hg, 1.5+/-0.3 mm Hg, and 2.9+/-0.7 mm Hg following the 0.5%, 1%, and 2% concentrations, respectively (P<0.05). Both the magnitude and duration of the ocular hypotensive effect of 0.5% flunarizine were enhanced with twice-daily administration for 5 days. Outflow facility in normal monkey eyes was increased (P<0.05) by 39% in the treated eyes compared with vehicle-treated contralateral eyes and by 41% compared with baseline values, and aqueous humor flow rates were unchanged (P>0.30).

CONCLUSIONS

Flunarizine reduces IOP in a dose-dependent manner when administered to glaucomatous monkey eyes, but also has an ocular hypotensive effect on the contralateral untreated eyes. An increase in tonographic outflow facility seems to account for the IOP reduction in normal monkey eyes.

摘要

目的

评估非选择性钙通道阻滞剂氟桂利嗪对激光诱导的单侧青光眼猴子眼压（IOP）以及正常猴子房水动力学的影响。

方法

对8只单侧激光诱导青光眼猴子的患眼单剂量给予0.5%、1%或2%氟桂利嗪，给药前及给药后每小时测量眼压，持续6小时。在另一项多剂量研究中，对同8只猴子的患眼连续5天每日两次应用0.5%氟桂利嗪。在未治疗的基线、仅用赋形剂治疗后以及治疗第1、3和5天测量眼压。对7只正常猴子每日两次给予0.5%氟桂利嗪，在第五次给药前后测量眼压描记流出系数和房水荧光光度流速。

结果

单侧应用50 μL的0.5%、1%或2%氟桂利嗪可使双侧眼压降低。在治疗的青光眼患眼中，氟桂利嗪使眼压分别降低2、3或5小时，0.5%、1%和2%浓度时最大降低幅度分别为2.5±0.5（均值±标准误）mmHg（9%）、3.0±0.4 mmHg（10%）和5.0±0.8 mmHg（18%）（P<0.01）。对侧未治疗眼在0.5%、1%和2%浓度时眼压最大降低幅度分别为1.3±0.5 mmHg、1.5±0.3 mmHg和2.9±0.7 mmHg（P<0.05）。0.5%氟桂利嗪每日两次给药5天，其降眼压作用的幅度和持续时间均增强。与赋形剂治疗的对侧眼相比，正常猴子患眼的流出系数增加（P<0.05），增加了39%，与基线值相比增加了41%，房水流量未改变（P>0.30）。