School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.
School of Mechanical Engineering, Purdue University, West Lafayette, IN 47906, United States.
Int J Pharm. 2024 Jan 25;650:123687. doi: 10.1016/j.ijpharm.2023.123687. Epub 2023 Dec 14.
Despite the growing popularity of subcutaneous (SC) administration for monoclonal antibodies (mAbs), there remains a limited understanding of the significance of mAb transport rate constants within the interstitial space and the lymphatic system on their pharmacokinetics. To bridge this knowledge gap, we introduce a compartmental model for subcutaneously administered mAbs. Our model differentiates FcRn-expressing cells across various sites, and the model predictions agree with experimental data from both human and rat studies. Our findings indicate that the time to reach the maximum mAb concentration in the plasma, denoted by T, displays a weak positive correlation with mAb half-life and a negligible correlation with bioavailability. In contrast, the half-life of mAbs exhibits a strong positive correlation with bioavailability. Moreover, the rate of mAb transport from lymph to plasma significantly affects the mAb half-life. Increasing the transport rates of mAbs from the injection site to the lymph or from lymph to plasma enhances bioavailability. These insights, combined with our compartmental model, contribute to a deeper understanding of the pharmacokinetics of subcutaneously administered mAbs.
尽管皮下（SC）给药已广泛应用于单克隆抗体（mAbs），但对于 mAbs 在细胞间和淋巴系统中的转运速率常数对其药代动力学的影响，仍存在有限的认识。为弥补这一知识空白，我们引入了一个用于皮下给药 mAbs 的房室模型。我们的模型区分了不同部位表达 FcRn 的细胞，模型预测与来自人体和大鼠研究的实验数据吻合。研究结果表明，达到血浆中最大 mAb 浓度的时间（T）与 mAb 半衰期呈弱正相关，与生物利用度几乎没有相关性。相比之下，mAb 的半衰期与生物利用度呈强正相关。此外，mAb 从淋巴到血浆的转运速率显著影响 mAb 的半衰期。增加 mAbs 从注射部位到淋巴或从淋巴到血浆的转运速率可提高生物利用度。这些发现与我们的房室模型相结合，有助于深入了解皮下给药 mAbs 的药代动力学。
