A comprehensive review of 20 years of progress in nonclinical QT evaluation and proarrhythmic assessment [0.03%]
过去20年非临床QT评价和抗心律失常评估的全面回顾
Eric Delpy,Anne-Marie Bétat,Annie Delaunois et al.
Eric Delpy et al.
The assessment of drug-induced QT interval prolongation and associated proarrhythmic risks, such as Torsades de Pointes (TdP), has evolved significantly over the past decades. This review traces the development of nonclinical QT evaluation,...
Géraldine Cellière,Andreas Krause,Guillaume Bonnefois et al.
Géraldine Cellière et al.
The white-paper regression model is the standard method for assessing QT liability of drugs. The quantity of interest, placebo-corrected QTc change from baseline (ΔΔQTc) with corresponding confidence interval (CI), is derived from the dif...
Gilberto Padilla Mercado,Christopher Cook,Norman Adkins et al.
Gilberto Padilla Mercado et al.
Toxicokinetic and pharmacokinetic (PK) summary parameters, such as Cmax (peak concentration), AUC (time-integrated area under the plasma concentration curve), and t1/2 (elimination half-life from the body), are important information for und...
Leveraging large language models to compare perspectives on integrating QSP and AI/ML [0.03%]
利用大型语言模型比较关于整合QSP和AI/ML的视角
Ioannis P Androulakis,Limei Cheng,Carolyn R Cho et al.
Ioannis P Androulakis et al.
Two recent papers offer contrasting perspectives on integrating Quantitative Systems Pharmacology (QSP) and Artificial Intelligence/Machine Learning (AI/ML): one views QSP as the primary driver using AI/ML to enhance computational tasks, wh...
Van Thuy Truong,Paolo Vicini,James Yates et al.
Van Thuy Truong et al.
Standard pharmacodynamic models are ordinary differential equations without the features of stochasticity and heterogeneity. We develop and analyse a stochastic model of a heterogeneous tumour-cell population treated with a drug, where each...
A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates [0.03%]
基于抗体药物偶联物的MMAE的 translational生理药代动力学模型
Hsuan-Ping Chang,Dhaval K Shah
Hsuan-Ping Chang
The objective of this work was to develop a translational physiologically-based pharmacokinetic (PBPK) model for antibody-drug conjugates (ADCs), using monomethyl auristatin E (MMAE)-based ADCs. A previously established dual-structured whol...
Diffusion dimensionality modeling of subcutaneous/intramuscular absorption of antibodies and long-acting injectables [0.03%]
基于扩散维度的皮下/肌内递药吸收模型研究抗体和长效注射剂
Murali Ramanathan,Wojciech Krzyzanski
Murali Ramanathan
To evaluate the role of diffusion process dimensionality in drug absorption following subcutaneous or intramuscular administration. The diffusion dimensionality model is based on analytical solutions of the 1-, 2- or 3-dimensional diffusion...
Machine learning approaches for assessing medication transfer to human breast milk [0.03%]
机器学习方法评估药物向人类乳汁转移情况
Zhongyuan Zhao,Peng Zou,Yuan Fang et al.
Zhongyuan Zhao et al.
The human milk/plasma (M/P) drug concentration ratio is crucial in pharmacology, especially for breastfeeding mothers undergoing treatment. It determines the extent to which drugs ingested by the mother pass into breast milk, potentially af...
Predicting tumor dynamics in treated patients from patient-derived-xenograft mouse models: a translational model-based approach [0.03%]
基于患者的异种移植小鼠模型预测治疗患者的肿瘤动态：一种转化的建模方法
D Ronchi,E M Tosca,P Magni
D Ronchi
This study presents a translational modeling framework designed to predict tumor size dynamics in cancer patients undergoing anticancer treatment, using data from patient-derived xenograft (PDX) mice. In the first step, a population tumor g...
Interoccasion variability in population pharmacokinetic models: identifiability, influence, interdependencies and derived study design recommendations [0.03%]
人群药代动力学模型中的机会间变异：可识别性、影响、相互依赖关系及由此派生的研究设计建议
Emily Behrens,Sebastian G Wicha
Emily Behrens
Modeling interoccasion variability (IOV) of pharmacokinetic parameters is challenging in sparse study designs. We conducted a simulation study with stochastic simulation and estimation (SSE) to evaluate the influence of IOV (25, 75%CV) from...