眼用药物药代动力学模型研究进展

Research progress of pharmacokinetic model of ophthalmic drugs

视力与生活质量息息相关。临床上倾向于使用侵入性较小的外用和全身给药方式治疗青光眼等眼部常见疾病。眼部许多的生理生化屏障包括泪液周转、角膜渗透、血-眼屏障等,限制药物在眼部的渗透与分布,造成眼内药代动力学特征不明确,常用眼部房室模型来描述药物在眼内处置动力学。经典眼房室模型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,而基于生理的药代动力学(PBPK)模型则引入眼部血流量变化、转运体对药物转运影响、血-眼屏障等因素,可提供更多药物在眼部的处置细节,有助于辅助眼用新药的开发和指导眼部疾病药物治疗。文章综述了不同给药方式时眼部用药的药代动力学特征,经典房室模型和PBPK模型及其在临床眼部用药方案设计中的应用。

Vision is closely tied to quality of life.Traditional drug delivery routes for clinical therapy of key ocular diseases,such as glaucoma,are topical and systemic administrations,which are less invasive but often face some physiological barriers such as tear film turnover,corneal penetration,and blood-ocular barrier.These barriers may limit penetration and distribution of ophthalmic drugs,resulting in limitation of information about pharmacokinetic characteristics of drugs in human eye.To address this,some ocular based compartment models,including classical ocular compartmental model and physiologically based pharmacokinetic(PBPK)model,have been established to illustrate dispositions of drugs in eyes.For classical ocular compartmental model,cornea or vitreous humor serves as central compartment and other ocular tissues are identified as peripheral compartments.The PBPK model,incorporating dynamic factors such as changes in ocular blood flow,effects of transporters,blood-ocular barrier,may characterize complex ocular physiology structure and dispositions of drugs in eyes.These models can contribute to development of new ophthalmic drugs and therapy strategies for ocular diseases.Here,the characteristics of drugs in eye following administrations via various routes,general ocular compartmental model and PBPK model as well as their applications in the development of new ophthalmic drugs and drug regimen for ocular diseases are reviened.