Anne V. Goldberg Glaucoma Service, Willis Eye Institute, Philadelphia, PA, USA.
J Ocul Pharmacol Ther. 2012 Apr;28(2):134-45. doi: 10.1089/jop.2011.0097. Epub 2011 Dec 2.
This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration-activity relationships.
Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry.
Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body.
Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.
本研究旨在通过单次局部给予 0.03%贝美前列素或 0.005%拉坦前列素治疗的患者的房水、角膜、巩膜、虹膜和睫状体中检测贝美前列素、拉坦前列素及其酸水解产物的分布，以了解浓度-活性关系。
31 例因眼球内肿瘤而接受眼球摘除术的患者，在术前 1、3、6 或 12 小时随机接受贝美前列素或拉坦前列素治疗。采用液相色谱-串联质谱法检测人房水和眼组织中贝美前列素、贝美前列素酸、拉坦前列素和拉坦前列素酸的浓度。
局部应用后，完整的贝美前列素在人眼中的分布顺序为角膜/巩膜＞虹膜/睫状体＞房水。这些组织中也检测到了贝美前列素酸，其在角膜中的水平相对较低，表明贝美前列素的水解有限。拉坦前列素是一种前体药物，主要通过角膜途径进入眼睛。拉坦前列素酸的水平分布为角膜＞房水＞虹膜＞巩膜＞睫状体。
本研究提供了实验证据，表明需要了解贝美前列素在相关眼组织中的水平，而不仅仅是房水中的水平，才能理解贝美前列素在人体中降低眼内压（IOP）的机制。数据表明，贝美前列素到达有利于结膜/巩膜吸收途径的靶组织。在靶睫状体中发现完整的贝美前列素表明其直接参与降低 IOP。然而，基于贝美前列素的降眼压效果大于拉坦前列素，而贝美前列素酸的水平在房水和角膜中仅为拉坦前列素酸水平的一小部分，且仅在睫状体中偶尔检测到，因此其可能只有有限的作用。在本报告中，同时检测了人眼组织和房水，以研究贝美前列素、贝美前列素酸、拉坦前列素和拉坦前列素酸在体内的分布。
