眼用药物药代动力学模型研究进展
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中国药科大学

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国家自然科学基金项目(面上项目,重点项目,重大项目)


Research progress of pharmacokinetic model of ophthalmic drugs
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China Pharmaceutical University

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    摘要:

    视力与生活质量息息相关,常发生于眼部的疾病包括年龄相关性黄斑变性、青光眼、糖尿病视网膜病。临床治疗倾向于使用侵入性较小的外用给药方式和全身给药方式。眼部许多的生理生化屏障包括泪膜周转、角膜渗透、血眼屏障等,限制药物在眼部的渗透与分布,造成药物的生物利用度较低,影响临床药物疗效。由于取样困难,药物在人眼中的药代动力学特征尚不清楚,因此建立眼部房室模型,一般以角膜或玻璃体为中央室,将眼部其他组织整体视为外周室,模拟研究药物在眼部的暴露量,可帮助预测药物在眼部的生物利用度和疗效。以此为基础,建立基于生理的药代动力学模型,如添加眼部血流量变化、转运体对药物转运影响、血-视网膜屏障、血-房水屏障等影响因素,可提供更多药物在眼部的处置细节,进而可以辅助眼用新药的开发,更好地治疗眼部疾病。

    Abstract:

    Vision is closely related to quality of life with age-related macular degeneration, glaucoma, and diabetic retinopathy commonly happening. Clinical treatment tends to use less invasive topical administration and systemic administration. Many physiological and biochemical obstacles in the eye, including tear film turnover, corneal penetration, blood-ocular barrier and so on, limit the penetration and distribution of drugs in the eye, resulting in low bioavailability of drugs and affecting the clinical drugs efficacy. Due to the difficulty of sampling, the pharmacokinetic characteristics of drugs in the human eye are still unclear. Therefore, establishing an ocular compartment model, typically considering the cornea or vitreous as the central compartment and treating other ocular tissues as the peripheral compartment, can simulate and study the drug exposure in the eye, which helps predict the bioavailability and therapeutic effect of drugs in the eye. Based on this, developing a physiologically-based pharmacokinetic model, which includes factors like changes in ocular blood flow, transporter effects on drug transport, blood-retinal barrier, blood-aqueous barrier, etc., can provide more details on the disposition of drugs in the eye, thereby assisting in the development of new ophthalmic drug and better treating eye diseases.

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  • 收稿日期:2024-02-29
  • 最后修改日期:2024-04-22
  • 录用日期:2024-04-22
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