Vadlapatla Ramya Krishna, Vadlapudi Aswani Dutt, Pal Dhananjay, Mitra Ashim K
University of Missouri- Kansas City, School of Pharmacy, 2464 Charlotte Street, Kansas City, MO 64108-2718, USA.
Curr Drug Metab. 2014;15(7):680-93. doi: 10.2174/1389200215666140926152459.
Ocular disorders can significantly lower a patient's quality of life. Centers for Disease Control and Prevention's Vision Health Initiative have estimated that the number of people affected by age-related ocular diseases may be doubled in the United States by 2030. Although availability of newer therapeutics has improved the prognosis of ocular diseases, poor ocular bioavailability still remains a major concern. Combinations of pharmacodynamic and pharmacokinetic barriers have been known to determine the amount of drug delivered to the target tissue. However, presence of membrane transporters and metabolizing enzymes pose a significant challenge to ocular drug disposition. Scientific literature confirms the expression of efflux/ATP-binding cassette transporters, influx/solute carrier transporters and several metabolic enzymes including oxidoreductases, hydrolases and transferases in different ocular tissues. Therefore, this review article describes the anatomical features of the eye and various barriers regulating ocular drug disposition. Differential expression of membrane transporters and metabolizing enzymes in normal and diseased states are briefly discussed. Further, the significance of transporter- metabolism interplay in ophthalmic drug design and various ocular drug delivery strategies are also outlined.
眼部疾病会显著降低患者的生活质量。美国疾病控制与预防中心的视力健康倡议组织估计，到2030年，美国受年龄相关性眼部疾病影响的人数可能会翻倍。尽管新型疗法的出现改善了眼部疾病的预后，但较差的眼部生物利用度仍是一个主要问题。已知药效学和药代动力学屏障的组合决定了输送到靶组织的药物量。然而，膜转运蛋白和代谢酶的存在对眼部药物处置构成了重大挑战。科学文献证实，不同眼部组织中存在外排/ATP结合盒转运蛋白、内流/溶质载体转运蛋白以及几种代谢酶，包括氧化还原酶、水解酶和转移酶。因此，这篇综述文章描述了眼睛的解剖特征以及调节眼部药物处置的各种屏障。简要讨论了正常和患病状态下膜转运蛋白和代谢酶的差异表达。此外，还概述了转运体-代谢相互作用在眼科药物设计中的意义以及各种眼部给药策略。
