Department of Applied Mathematics, Israeli Institute for Biological Research, PO Box 19, 7410001, Ness-Ziona, Israel.
, Ness-Ziona, Israel.
Sci Rep. 2023 Sep 22;13(1):15869. doi: 10.1038/s41598-023-42878-5.
Levodopa is currently the standard of care treatment for Parkinson's disease, but chronic therapy has been linked to motor complications. Designing a controlled release formulation (CRF) that maintains sustained and constant blood concentrations may reduce these complications. Still, it is challenging due to levodopa's pharmacokinetic properties and the notion that it is absorbed only in the upper small intestine (i.e., exhibits an "absorption window"). We created and validated a physiologically based mathematical model to aid the development of such a formulation. Analysis of experimental results using the model revealed that levodopa is well absorbed throughout the entire small intestine (i.e., no "absorption window") and that levodopa in the stomach causes fluctuations during the first 3 h after administration. Based on these insights, we developed guidelines for an improved CRF for various stages of Parkinson's disease. Such a formulation is expected to produce steady concentrations and prolong therapeutic duration compared to a common CRF with a smaller dose per day and a lower overall dose of levodopa, thereby improving patient compliance with the dosage regime.
左旋多巴目前是治疗帕金森病的标准治疗方法，但慢性治疗与运动并发症有关。设计一种控释制剂（CRF），使其保持持续和恒定的血液浓度，可能会减少这些并发症。然而，由于左旋多巴的药代动力学特性以及它仅在上段小肠吸收（即表现出“吸收窗”）的概念，这是具有挑战性的。我们创建并验证了一个基于生理学的数学模型，以帮助开发这种制剂。使用该模型对实验结果进行分析表明，左旋多巴在整个小肠中都能很好地被吸收（即没有“吸收窗”），并且胃中的左旋多巴在给药后 3 小时内引起波动。基于这些见解，我们为帕金森病的各个阶段制定了改进型 CRF 的指南。与每天剂量较小且总左旋多巴剂量较低的常见 CRF 相比，这种制剂预计会产生稳定的浓度并延长治疗持续时间，从而提高患者对剂量方案的依从性。
