A Comprehensive Physiologically Based Pharmacokinetic Model for Predicting Vildagliptin Pharmacokinetics: Insights into Dosing in Renal Impairment

Pharmaceuticals Pub Date : 2024-07-10 DOI:10.3390/ph17070924
Mahnoor Pasha, Ammara Zamir, M. Rasool, Hamid Saeed, Tanveer Ahmad, N. S. Alqahtani, Lamya Saif Alqahtani, F. Alqahtani
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Abstract

Physiologically based pharmacokinetic (PBPK) modeling is of great importance in the field of medicine. This study aims to construct a PBPK model, which can provide reliable drug pharmacokinetic (PK) predictions in both healthy and chronic kidney disease (CKD) subjects. To do so, firstly a review of the literature was thoroughly conducted and the PK information of vildagliptin was collected. PBPK modeling software, PK-Sim®, was then used to build and assess the IV, oral, and drug-specific models. Next, the average fold error, visual predictive checks, and predicted/observed ratios were used for the assessment of the robustness of the model for all the essential PK parameters. This evaluation demonstrated that all PK parameters were within an acceptable limit of error, i.e., 2 fold. Also to display the influence of CKD on the total and unbound AUC (the area under the plasma concentration–time curve) and to make modifications in dose, the analysis results of the model on this aspect were further examined. This PBPK model has successfully depicted the variations of PK of vildagliptin in healthy subjects and patients with CKD, which can be useful for medical practitioners in dosage optimization in renal disease patients.
用于预测维达列汀药代动力学的基于生理学的综合药代动力学模型:肾功能不全患者用药的启示
基于生理学的药代动力学(PBPK)建模在医学领域具有重要意义。本研究旨在构建一个 PBPK 模型,该模型可对健康和慢性肾脏病(CKD)受试者进行可靠的药物药代动力学(PK)预测。为此,首先对文献进行了全面回顾,并收集了维达列汀的 PK 信息。然后使用 PBPK 建模软件 PK-Sim®,建立并评估静脉注射、口服和药物特异性模型。然后,使用平均折叠误差、视觉预测检查和预测/观察比值来评估所有重要 PK 参数模型的稳健性。评估结果表明,所有 PK 参数都在可接受的误差范围内,即 2 倍。此外,为了显示慢性肾功能衰竭对总AUC和非结合AUC(血浆浓度-时间曲线下面积)的影响并对剂量进行调整,还进一步检查了模型在这方面的分析结果。该PBPK模型成功地描述了维达列汀在健康受试者和CKD患者中的PK变化,有助于医生对肾病患者进行剂量优化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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