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局部用与缓释比马前列素的眼压效应及作用机制

Intraocular Pressure Effects and Mechanism of Action of Topical Versus Sustained-Release Bimatoprost.

作者信息

Lee Susan S, Almazan Alexandra, Decker Sherri, Zhong Yan, Ghebremeskel Alazar N, Hughes Patrick, Robinson Michael R, Burke James A, Weinreb Robert N

机构信息

Allergan plc, Irvine, CA, USA.

Hamilton Glaucoma Center, Shiley Eye Institute and Department of Ophthalmology, University of California San Diego, La Jolla, CA, USA.

出版信息

Transl Vis Sci Technol. 2019 Jan 30;8(1):15. doi: 10.1167/tvst.8.1.15. eCollection 2019 Jan.

Abstract

PURPOSE

To assess the intraocular pressure (IOP)-lowering effects of bimatoprost sustained-release implant (BimSR) in normotensive monkeys receiving topical bimatoprost.

METHODS

Six eyes from six female, normotensive, cynomolgus monkeys were treated with once-daily topical latanoprost 0.005% plus twice-daily fixed-combination dorzolamide 2%/timolol 0.5%. At week 5, topical latanoprost was switched to once-daily topical bimatoprost 0.03% and twice-daily dorzolamide 2%/timolol 0.5% was continued. At week 8, BimSR 20 μg was administered intracamerally to three eyes and topical therapy was continued in all eyes. At week 12, all topical therapy was discontinued and animals were monitored for another 4 weeks. IOP was measured with a TonoVet rebound tonometer in nonsedated animals weekly for 16 weeks.

RESULTS

Average mean (standard deviation) IOP was 19.8 (1.6) mm Hg at baseline, 15.7 (0.9) mm Hg during treatment with topical latanoprost/dorzolamide/timolol from weeks 1 to 5, and 14.2 (0.5) mm Hg during weeks 6 to 8 after topical latanoprost was switched to topical bimatoprost. After BimSR was added, average mean IOP during weeks 9 to 12 was 10.8 (1.3) mm Hg, a decrease of 3.9 mm Hg compared with the topical-only arm. When topical therapy was discontinued, IOP in BimSR-treated eyes remained below that in unmedicated eyes (15.8 [0.9] vs. 20.2 [0.2] mm Hg at weeks 14-16).

CONCLUSIONS

Intracameral BimSR has IOP-lowering effects additive to those of topical bimatoprost, suggesting an additional mechanism of action with intracameral drug delivery.

TRANSLATIONAL RELEVANCE

Compared with topical bimatoprost, intracameral BimSR may have an additional mechanism of action of IOP lowering.

摘要

目的

评估比马前列素缓释植入剂(BimSR)对接受局部用比马前列素治疗的正常血压猴的眼压(IOP)降低作用。

方法

对6只雌性正常血压食蟹猴的6只眼睛,每天一次局部使用0.005%拉坦前列素,同时每天两次使用固定复方制剂2%多佐胺/0.5%噻吗洛尔。在第5周时,将局部用拉坦前列素换成每天一次局部使用0.03%比马前列素,并继续每天两次使用2%多佐胺/0.5%噻吗洛尔。在第8周时,对3只眼睛进行前房内注射20μg BimSR,并继续对所有眼睛进行局部治疗。在第12周时,停止所有局部治疗,并对动物再监测4周。使用TonoVet回弹眼压计每周对未麻醉动物测量眼压,持续16周。

结果

基线时平均(标准差)眼压为19.8(1.6)mmHg,在第1至5周局部使用拉坦前列素/多佐胺/噻吗洛尔治疗期间为15.7(0.9)mmHg,在局部用拉坦前列素换成局部用比马前列素后的第6至8周为14.2(0.5)mmHg。添加BimSR后,第9至12周的平均眼压为10.8(1.3)mmHg,与仅局部用药组相比降低了3.9mmHg。当停止局部治疗时,接受BimSR治疗的眼睛的眼压仍低于未用药眼睛的眼压(第14 - 16周时分别为15.8 [0.9] vs. 20.2 [0.2] mmHg)。

结论

前房内注射BimSR具有降低眼压的作用,是局部用比马前列素降低眼压作用的附加作用,提示前房内给药存在额外的作用机制。

转化相关性

与局部用比马前列素相比,前房内注射BimSR可能具有额外的降低眼压作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62c3/6355114/428428e1abbe/i2164-2591-8-1-15-f01.jpg

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