Institute for Systems Medicine with Focus on Organ Interaction, University Hospital RWTH Aachen, Aachen, Germany.
Institute for Biostatistics and Informatics in Medicine and Aging Research (IBIMA), Rostock University Medical Center, Rostock, Germany.
CPT Pharmacometrics Syst Pharmacol. 2023 Mar;12(3):288-299. doi: 10.1002/psp4.12918. Epub 2023 Jan 27.
Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant healthcare burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PKs) and pharmacodynamics (PDs). Ocular quantitative systems pharmacology models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based PK (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models using molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eyes and discuss cellular systems, data repositories, as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for postoperative fibrosis after glaucoma surgery.
良好的视力属于健康最有价值的属性之一,眼部疾病是一个重大的医疗保健负担。由于人口老龄化,预计未来几十年病例数量将进一步增加。然而,由于眼部给药和药物药代动力学 (PKs) 和药效动力学 (PDs) 组织取样的限制,眼科药物的开发具有一定难度。眼部定量系统药理学模型提供了描述药物在眼部的分布以及在眼部特定部位的药物反应的机会。特别是,需要眼部生理 PK (PBPK) 模型来描述眼部不同区域的药物浓度水平。此外,还需要使用特定细胞系统的分子数据的眼部效应模型来开发剂量反应相关性。在这里,我们描述了眼部 PK/PBPK 以及 PD 模型的当前状态,并讨论了眼科中的细胞系统、数据库以及动物模型。各种概念的应用重点是开发青光眼手术后术后纤维化的新治疗方法。