Physiologically-based pharmacokinetic model for predicting drug-drug interactions perpetrated by posaconazole in healthy subjects with normal weight and obesity: Concomitant use and washout [0.03%]
基于生理的药代动力学模型预测波西康唑在正常体重和肥胖受试者中与其他药物相互作用：联用及清除期研究
Christopher D Bruno,Ahmed Elmokadem,David J Greenblatt et al.
Christopher D Bruno et al.
Posaconazole is an effective broad-spectrum triazole antifungal used as prophylaxis or to treat invasive Aspergillus and Candida infections in adults and pediatric patients. Posaconazole is a known strong inhibitor of cytochrome P4503A4 (CY...
Using Fisher Information Matrix to predict uncertainty in covariate effects and power to detect their relevance in Non-Linear Mixed Effect Models in pharmacometrics [0.03%]
利用费雪信息矩阵预测协变量效应的不确定性以及在非线性混合效应模型中检测其相关性的功效
Lucie Fayette,Karl Brendel,France Mentré
Lucie Fayette
This work focuses on design of experiments for Pharmacokinetic (PK) and Pharmacodynamic (PD) studies. Non-Linear Mixed Effects Models (NLMEM) modelling allows the identification and quantification of covariates that explain inter-individual...
FDA's insights: implementing new strategies for evaluating drug-induced QTc prolongation [0.03%]
美国食品药品管理局的见解：实施评估药物所致QT间期延长的新策略
Yanyan Ji,Lars Johannesen,Christine Garnett
Yanyan Ji
The questions and answers (Q&A) document for ICH E14/S7B provides the following advancements for QTc assessment: concentration-QTc modeling (C-QTc) as the primary analysis, accepting alternative approaches (Q&A 5.1 and 6.1) to thorough QT (...
The dawn of a new era: can machine learning and large language models reshape QSP modeling? [0.03%]
新时代的曙光：机器学习和大型语言模型能否重塑QSP建模？
Ioannis P Androulakis,Lourdes Cucurull-Sanchez,Anna Kondic et al.
Ioannis P Androulakis et al.
Quantitative Systems Pharmacology (QSP) has emerged as a cornerstone of modern drug development, providing a robust framework to integrate data from preclinical and clinical studies, enhance decision-making, and optimize therapeutic strateg...
Cross-species translational modelling of targeted therapeutic oligonucleotides using physiologically based pharmacokinetics [0.03%]
基于生理的药代动力学在靶向治疗寡核苷酸跨物种转化模型中的应用
Abdallah Derbalah,Felix Stader,Cong Liu et al.
Abdallah Derbalah et al.
Oligonucleotide therapeutics hold promise for targeted gene silencing, yet achieving optimal tissue-specific delivery remains challenging. This study introduces a mechanistic whole-body physiologically based pharmacokinetic (PBPK) model to ...
Leveraging large language models in pharmacometrics: evaluation of NONMEM output interpretation and simulation capabilities [0.03%]
利用大型语言模型进行药代动力学研究：NONMEM输出解释和模拟能力评估
Hwa Jun Cha,Kyuyeon Choe,Euibeom Shin et al.
Hwa Jun Cha et al.
Advancements in large language models (LLMs) have suggested their potential utility for diverse pharmacometrics tasks. This study investigated the performance of LLM for generating structure diagrams, publication-ready tables, analysis repo...
Interplay between pharmacokinetics and immunogenicity of therapeutic proteins: stepwise development of a bidirectional joint pharmacokinetics-anti-drug antibodies model [0.03%]
治疗性蛋白质的药代动力学和免疫原性的相互作用：双向联合药代动力学-抗药物抗体模型的逐步开发
Jan-Stefan van der Walt,Justin Wilkins,Akash Khandelwal et al.
Jan-Stefan van der Walt et al.
The aim of the analysis was to develop a phenomenological longitudinal population pharmacokinetics (PK)-anti-drug antibodies (ADA) model to enable an informed and quantitative framework for assessment of ADA influence. Data used were from s...
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...