Garimella Harsha T, Norris Carly, German Carrie, Przekwas Andrzej, Walenga Ross, Babiskin Andrew, Tan Ming-Liang
Biomedical, Energy, and Materials Division, CFD Research Corporation, 6820 Moquin Drive NW, Huntsville, AL 35806, USA.
Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Bioengineering (Basel). 2025 Jul 30;12(8):825. doi: 10.3390/bioengineering12080825.
Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug's distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions.
局部给药是将药物递送至眼部以治疗各种眼部疾病（包括青光眼、干眼症和炎症）的常用方法。局部给药后的药物疗效，包括药物在眼内的分布、吸收和消除速率以及生理反应，可以使用基于生理的药代动力学（PBPK）模型进行预测。为了改进药物递送的模拟，需要高分辨率的眼部计算模型；然而，这些方法可能运行时间较长。在本研究中，开发了一种快速运行的人体泪膜计算准三维（Q3D）模型，以考虑吸收、眨眼、引流和蒸发。使用这种Q3D方法可以实现对整个泪膜中眨眼力学和流动分布的可视化。基于常微分方程（ODE）系统，使用高分辨率隔室模型对整个泪膜子区域的平均药物吸收进行了量化。通过将模拟结果与泪膜中局部应用0.1%地塞米松混悬液的实验数据进行比较，对模拟进行了验证（R = 0.76，RMSE = 8.7，AARD = 28.8%）。总体而言，Q3D泪膜模型考虑了快速运行模型中以前未包括的关键机制因素（例如眨眼和引流）。此外，这项工作展示了提高计算效率的方法，即在保持准确性的同时减少了中央处理器（CPU）时间。基于这项工作，应用于泪膜的这种Q3D方法将允许更无缝地集成到全身模型中，这将是眼部疾病治疗开发中极其有价值的工具。
