Sheppard John D, Cockrum Paul C, Justice Angela, Jasek Mark C
Virginia Eye Consultants, Norfolk, VA, USA.
HealthKinetics, Fort Worth, TX, USA.
Ophthalmol Ther. 2018 Jun;7(1):157-165. doi: 10.1007/s40123-018-0130-1. Epub 2018 May 14.
Little is known of the ocular distribution characteristics of currently branded non-steroidal anti-inflammatory drugs (NSAIDs) in the United States. This study was designed to predict the ocular bioavailability characteristics in humans using Dutch Belted rabbits as a surrogate. Commercially available, topically-applied NSAIDs containing bromfenac or nepafenac/amfenac were evaluated.
126 healthy adult Dutch Belted rabbits were randomly assigned to three treatment cohorts (BromSite twice daily [BID] in the right eye, BromSite once daily [QD] in the right eye, Prolensa QD in the right eye and Ilevro™ QD in the left eye) and 7 post-dosing time points (0.5, 1, 2, 4, 8, 12, 24 h after final instillation). The study eyes received 40 µL of the assigned drug for a consecutive 9 days. Samples of aqueous humor, iris-ciliary body, choroid, sclera, and retina were harvested from the study eyes at the assigned time point after the last dose on the 9th day. NSAID content in ocular tissues was analyzed using high-performance liquid chromatography (HPLC), and area under the curve (AUC), maximum concentration (C), and time to maximum concentration (T) were determined.
Peak NSAID concentrations were reached within 1-3 h in the anterior segment and within 1-3 h in the posterior segment after last dose. Throughout the ocular tissues, both AUC and C for BromSite (BID and QD) were consistently higher than respective NSAID concentrations of Prolensa QD and Ilevro QD. When comparing BromSite BID to QD, the BID regimen produced generally higher but statistically similar bromfenac concentrations throughout the ocular tissues except in the aqueous humor and iris-ciliary body, where the AUC BID was statistically significantly higher with BromSite BID.
As a surrogate to human ocular bioavailability, BromSite demonstrated significantly greater NSAID compared to Prolensa QD and Ilevro QD. The DuraSite component of BromSite appears to enhance ocular penetration throughout both anterior and posterior tissues.
Sun Pharmaceutical Industries Ltd.
在美国，目前上市的非甾体抗炎药（NSAIDs）的眼部分布特征鲜为人知。本研究旨在以荷兰带兔作为替代模型，预测其在人体中的眼部生物利用度特征。对市售的含溴芬酸或萘非那酸/安芬那酸的局部应用NSAIDs进行了评估。
将126只健康成年荷兰带兔随机分为三个治疗组（右眼每日两次[BID]使用BromSite，右眼每日一次[QD]使用BromSite，右眼每日一次[QD]使用Prolensa，左眼每日一次[QD]使用Ilevro™），并设置7个给药后时间点（最后一次滴注后0.5、1、2、4、8、12、24小时）。研究眼连续9天接受40μL指定药物。在第9天最后一剂给药后的指定时间点，从研究眼中采集房水、虹膜睫状体、脉络膜、巩膜和视网膜样本。使用高效液相色谱（HPLC）分析眼组织中的NSAID含量，并测定曲线下面积（AUC）、最大浓度（C）和达最大浓度时间（T）。
最后一剂给药后，前节在1 - 3小时内达到NSAID峰值浓度，后节在1 - 3小时内达到峰值浓度。在整个眼组织中，BromSite（BID和QD）的AUC和C始终高于Prolensa QD和Ilevro QD各自的NSAID浓度。将BromSite BID与QD进行比较时，除房水和虹膜睫状体中BromSite BID的AUC在统计学上显著更高外，BID给药方案在整个眼组织中产生的溴芬酸浓度总体上更高，但在统计学上相似。
作为人体眼部生物利用度的替代模型，与Prolensa QD和Ilevro QD相比，BromSite显示出显著更高的NSAID含量。BromSite的DuraSite成分似乎可增强其在前节和后节组织中的眼部渗透。
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