Batool Maryam, Zamir Ammara, Alqhtani Hussain, Saeed Hamid, Rasool Muhammad Fawad
Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan.
Department of Clinical Pharmacy, College of Pharmacy, Najran University, 61441, Najran, Saudi Arabia.
Saudi Pharm J. 2025 Jul 9;33(4):24. doi: 10.1007/s44446-025-00024-4.
The physiologically based pharmacokinetic (PBPK) modeling is an in-silico technique that determines drug pharmacokinetics (PK) by considering blood circulation and tissue composition within the body. Fexofenadine is an H receptor antagonist drug recommended for treating seasonal allergic rhinitis and chronic idiopathic urticaria. This study aimed to build a PBPK model of fexofenadine to predict its systemic exposure in healthy, diseased, and pediatric populations. The modeling process commenced with a meticulous literature review to collect pertinent PK data on fexofenadine, which was then consolidated into the PK-Sim simulator to develop a drug-specific model in the healthy population. The model was then extrapolated to patients with chronic kidney disease (CKD) and pediatrics by employing disease and age-related physiological variations. Visual predictive checks were executed to substantiate the model's accuracy, along with the computation of observed-to-predicted ratios (R), average fold error (AFE), and absolute average fold error (AAFE). The developed PBPK model successfully predicted fexofenadine's PK with AFE values of 0.98, 0.58, and 1.21 for CL/F in healthy, diseased, and pediatric populations, which were confined within a two-fold error range. Furthermore, box-and-whisker plots were generated to critically analyze drug concentration at varying stages of CKD. The presented model offers indispensable insights that may assist clinicians in determining dosing strategies in patients with kidney disease.
基于生理的药代动力学（PBPK）建模是一种计算机模拟技术，它通过考虑体内血液循环和组织组成来确定药物的药代动力学（PK）。非索非那定是一种H受体拮抗剂药物，推荐用于治疗季节性过敏性鼻炎和慢性特发性荨麻疹。本研究旨在构建非索非那定的PBPK模型，以预测其在健康、患病和儿科人群中的全身暴露情况。建模过程始于细致的文献综述，以收集有关非索非那定的相关PK数据，然后将其整合到PK-Sim模拟器中，以在健康人群中开发特定药物模型。然后，通过采用与疾病和年龄相关的生理变化，将该模型外推至慢性肾脏病（CKD）患者和儿科患者。进行了视觉预测检查以证实模型的准确性，同时计算观察值与预测值之比（R）、平均倍数误差（AFE）和绝对平均倍数误差（AAFE）。所开发的PBPK模型成功预测了非索非那定的PK，健康、患病和儿科人群中CL/F的AFE值分别为0.98、0.58和1.21，均在两倍误差范围内。此外，还生成了箱线图，以严格分析CKD不同阶段的药物浓度。所提出的模型提供了不可或缺的见解，可能有助于临床医生确定肾病患者的给药策略。
