Allergan plc, Irvine, California.
J Ocul Pharmacol Ther. 2019 Apr;35(3):138-144. doi: 10.1089/jop.2018.0095. Epub 2019 Jan 30.
To compare the dose-response profiles of bimatoprost sustained-release implant (Bimatoprost SR) and topical bimatoprost in lowering intraocular pressure (IOP) in normotensive beagle dogs.
In 1 study, topical bimatoprost 0.001%, 0.01%, or 0.1% was administered twice daily in the study eye for 5 days. IOP was measured at baseline and up to hour 6 each day. Other studies evaluated the IOP response to a single administration of Bimatoprost SR at dose strengths ranging from 8 to 120 μg. IOP was measured before implant administration and during 3 months of follow-up; IOP in response to topical bimatoprost 0.03% was measured prestudy as an internal control.
Mean percentage decrease in IOP from baseline at hour 6 (peak effect) across study days was 15.7%, 36.1%, and 24.8% (2.8, 7.0, and 4.0 mmHg) in animals treated with topical bimatoprost 0.001%, 0.01%, and 0.1%, respectively. After Bimatoprost SR administration, mean percentage decrease in IOP from baseline across 3 months consistently increased with increasing dose strength and was 38.7% (7.2 mmHg) with Bimatoprost SR 120 μg. Mean percentage IOP decrease with topical bimatoprost 0.03% was 27.6% (5.9 mmHg).
Topical bimatoprost demonstrated a U-shaped dose-response curve; increasing the bimatoprost concentration to 0.1% resulted in reduced IOP-lowering efficacy. In contrast, the dose-response curve for Bimatoprost SR showed consistently greater IOP lowering as the dose strength increased, with the dose strength producing maximum IOP lowering not yet determined. At 60- and 120-μg dose strengths, Bimatoprost SR produced greater IOP reductions than were achieved with topical dosing.
比较贝美前列素持续释放植入物（Bimatoprost SR）和局部用贝美前列素降低正常眼压大白兔眼内压（IOP）的剂量反应曲线。
在一项研究中，研究眼局部应用 0.001%、0.01%或 0.1%的贝美前列素，每天两次，共 5 天。在基线和每天第 6 小时测量 IOP。其他研究评估了单次给予剂量强度范围为 8 至 120μg 的 Bimatoprost SR 对 IOP 的反应。在植入物给药前和 3 个月的随访期间测量 IOP；在研究前测量局部用贝美前列素 0.03%的 IOP 作为内部对照。
在第 6 小时（高峰效应），与基线相比，在接受局部用贝美前列素 0.001%、0.01%和 0.1%治疗的动物中，IOP 的平均百分比下降分别为 15.7%、36.1%和 24.8%（2.8、7.0 和 4.0mmHg）。在 Bimatoprost SR 给药后，3 个月内，IOP 从基线的平均百分比下降随着剂量强度的增加而持续增加，Bimatoprost SR 120μg 时为 38.7%（7.2mmHg）。局部用贝美前列素 0.03%的平均 IOP 下降百分比为 27.6%（5.9mmHg）。
局部用贝美前列素呈 U 形剂量反应曲线；将贝美前列素浓度增加到 0.1%会降低降眼压疗效。相比之下，Bimatoprost SR 的剂量反应曲线显示，随着剂量强度的增加，IOP 降低幅度持续增加，最大降 IOP 剂量强度尚未确定。在 60μg 和 120μg 剂量强度下，Bimatoprost SR 产生的 IOP 降低幅度大于局部给药。
