School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland.
Adv Drug Deliv Rev. 2018 Feb 15;126:3-22. doi: 10.1016/j.addr.2017.12.009. Epub 2017 Dec 14.
The eye is protected by several tissues that limit the permeability and entry of potentially harmful substances, but also hamper the delivery of drugs in the treatment of ocular diseases. Active transport across the ocular barriers may affect drug distribution, but the impact of drug transporters on ocular drug delivery is not well known. We have collected and critically reviewed the literature for ocular expression and activity of known drug transporters. The review concentrates on drug transporters that have been functionally characterized in ocular tissues or primary cells and on transporters for which there is available expression data at the protein level. Species differences are highlighted, since these may explain observed inconsistencies in the influence of specific transporters on drug disposition. There is variable evidence about the pharmacokinetic role of transporters in ocular tissues. The strongest evidence for the role of active transport is available for the blood-retinal barrier. We explored the role of active transport in the cornea and blood retinal barrier with pharmacokinetic simulations. The simulations show that the active transport is important only in the case of specific parameter combinations.
眼睛由多种组织保护，这些组织限制了潜在有害物质的通透性和进入，但也阻碍了眼部疾病治疗中药物的递送。主动跨眼部屏障转运可能会影响药物分布，但药物转运体对眼部药物递送的影响尚不清楚。我们已经收集并批判性地回顾了已知药物转运体在眼部表达和活性的文献。该综述集中于在眼部组织或原代细胞中具有功能特征的药物转运体，以及在蛋白质水平上具有可用表达数据的转运体。突出了物种差异，因为这些差异可能解释了特定转运体对药物处置的影响不一致。关于转运体在眼部组织中的药代动力学作用存在可变的证据。主动转运在血视网膜屏障中的作用有最强的证据。我们用药代动力学模拟探索了主动转运在角膜和血视网膜屏障中的作用。模拟表明，只有在特定参数组合的情况下，主动转运才是重要的。
