A note on phase I interleaved versus parallel group ascending dose designs for concentration-QTc analyses [0.03%]
关于浓度-QTc分析的升剂量期I交错设计与平行组设计的一点思考
Günter Heimann,Thomas Dumortier,Karin Meiser
Günter Heimann
PK-QTc analyses are an integral part of drug development programs. These analyses are often based on phase I study data, and the question may be asked whether the design of these phase I studies has an impact on the precision of the corresp...
QT interval prolongation: clinical assessment, risk factors and quantitative pharmacological considerations [0.03%]
心电图QT间期延长：临床评估、风险因素及定量药理学考虑
Verena Gotta,Birgit Donner
Verena Gotta
Prolongation of the QT interval in the ECG is a critical finding that signifies an extended duration from the onset of ventricular depolarization to the end of ventricular repolarization. It can predispose patients to life-threatening arrhy...
An automated pipeline to generate initial estimates for population Pharmacokinetic base models [0.03%]
用于人群药代动力学基础模型的初始估计的自动化流程构建
Zhonghui Huang,Matthew Fidler,Minshi Lan et al.
Zhonghui Huang et al.
Nonlinear mixed-effects models rely on adequate initial parameter estimates for efficient parameter optimization. Poor initial estimates can result in failed model convergence or termination with incorrect parameter estimates. Non-compartme...
Characterization of CAR-T cellular kinetics and efficacy in solid tumor patients with and without prior lymphodepletion chemotherapy using a PBPK-PD model [0.03%]
基于生理药代动力学( PBPK )和药效学模型的CAR-T细胞在有或无预淋巴耗竭化疗的实体瘤患者中的特征研究
Keyur R Parmar,Agnish Dey,Angelia F Wang et al.
Keyur R Parmar et al.
Despite tremendous clinical responses and patient benefit in hematological malignancies, chimeric Antigen Receptor (CAR) T cells have demonstrated limited success in solid tumors. Herein, we have scaled and augmented our previously describe...
Eric L Haseltine,Violeta Rodriguez-Romero
Eric L Haseltine
Solving models comprised of nonlinear differential equations (DEs) in NONMEM using ADVAN6 or ADVAN13 typically requires substantially longer run times than models comprised of linear DEs, which in some cases allow for analytical solutions. ...
A QSP PDE model of ADC transport and kinetics in a growing or shrinking tumor [0.03%]
用于描述ADC在生长或缩小的肿瘤中的转运和动力学的QSP偏微分方程模型
David S Ross,Antonio Cabal
David S Ross
When a tumor is treated with an antibody-drug conjugate (ADC) complex biochemistry occurs in a domain-the tumor-whose size and structure are changing. Some parts of the tumor may be growing because tumor cells proliferate. Other parts may b...
Scoping review of the role of pharmacometrics in model-informed drug development [0.03%]
药代动力学在基于模型的药物研发中的作用的综述研究
Amruta Gajanan Bhat,Euibeom Shin,Amit Roy et al.
Amruta Gajanan Bhat et al.
Model-informed drug development (MIDD) is a framework that utilizes quantitative modeling and simulation methods to integrate nonclinical and clinical data, as well as prior knowledge, to inform drug development and regulatory decision-maki...
Exposure-safety Markov modeling of ocular adverse events in patient populations treated with tisotumab vedotin [0.03%]
替西妥珠单抗治疗患者群体中眼部不良事件的暴露-安全性马尔可夫模型分析
Summer Feng,Rudy Gunawan,Chaitali Passey et al.
Summer Feng et al.
Tisotumab vedotin (TV), a tissue factor-directed antibody-drug conjugate (ADC), is approved in the US at 2.0 mg/kg every 3 weeks (Q3W) for adult patients with recurrent or metastatic cervical cancer following disease progression on or after...
Impact of covariate model building methods on their clinical relevance evaluation in population pharmacokinetic analyses: comparison of the full model, stepwise covariate model (SCM) and SCM+ approaches - further results based on more conventional practices [0.03%]
协变量模型构建方法对群体药代动力学分析中临床相关性评估的影响：全模型、逐步协变量模型(SCM)和SCM+方法的比较-基于更多传统实践的进一步结果
Morgane Philipp,Simon Buatois,Sylvie Retout et al.
Morgane Philipp et al.
Covariate clinical relevance (CCR) is commonly assessed in population pharmacokinetics using forest plots visualizing parameter changes across covariate values. In our previous work (Philipp et al. 2024), CCR was evaluated using a [0.80-1.2...
Rong Chen,Mark Sale,Alex Mazur et al.
Rong Chen et al.
Automatic differentiation (AD), a key method for accurately and efficiently computing derivatives in modern machine learning, is now implemented in Phoenix® NLME™ 8.6 for the first time and applied to the first-order conditional estimatio...