Target-Mediated Drug Disposition Revisited: Michaelis-Menten Approximations for Bivalent Drug Molecules [0.03%]
重温以靶点为介导的药物处置：二价药物分子的米氏方程近似
Ronny Straube
Ronny Straube
The Michaelis-Menten (MM) approximation of the target-mediated drug disposition (TMDD) model is often used to describe nonlinear pharmacokinetics of monoclonal antibodies, which are, however, bivalent molecules. We analyze a TMDD model for ...
Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling [0.03%]
基于生理的药代动力学模型预测波生坦系统的和肝脏暴露量
Miao-Chan Huang,Julia Macente,Sofie Heylen et al.
Miao-Chan Huang et al.
Bosentan is the first approved oral medication for pulmonary arterial hypertension, yet the black-box warning on its labeling implies a substantial risk of liver injury associated with bosentan exposure. The risk assessment of bosentan-indu...
A Pharmacometrics-Informed Trial Simulation Framework for Optimizing Study Designs for Disease-Modifying Treatments in Rare Neurological Disorders [0.03%]
基于药代动力学的试验模拟框架，用于优化罕见神经系统疾病改良治疗研究的设计
Yevgen Ryeznik,Ralf-Dieter Hilgers,Nicole Heussen et al.
Yevgen Ryeznik et al.
The development of new treatments for rare neurological diseases (RNDs) may be very challenging due to limited natural history data, lack of relevant biomarkers and clinical endpoints, small and heterogeneous patient populations, and other ...
A Case Study of Model-Informed Drug Development of a Novel PCSK9 Antisense Oligonucleotide. Part 2: Phase 2 to Phase 3 [0.03%]
基于模型的新型PCSK9寡核苷酸药物开发案例研究（第二部分：从II期到III期）
Jane Knöchel,Catarina Nilsson,Björn Carlsson et al.
Jane Knöchel et al.
In this second part of a case study on the practical use of model-informed drug development (MIDD), we describe the clinical development of AZD8233, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide, fr...
Assessing Cytochrome P450 Drug Interaction Risk for Dordaviprone Using Physiologically Based Pharmacokinetic Modeling [0.03%]
基于生理的药代动力学模型评估Dordaviprone药物相互作用的细胞色素P450风险
Swati Jaiswal,Nikunjkumar K Patel,Hannah M Jones et al.
Swati Jaiswal et al.
A physiologically based pharmacokinetic (PBPK) model was developed and verified for dordaviprone, a small molecule with antitumor effects in glioma patients. The model was applied to assess the drug-drug interaction (DDI) potential of dorda...
Model-Informed Precision Dosing of Infliximab in Korean Inflammatory Bowel Disease Patients: External Validation of Population Pharmacokinetic Models [0.03%]
基于人群药代动力学模型的英夫利西单抗个体化剂量在韩国炎症性肠病患者中的外部验证研究
Yoonjin Kim,Seung Hwan Baek,In-Jin Jang et al.
Yoonjin Kim et al.
Underexposure to infliximab often leads to loss of response in patients with inflammatory bowel disease (IBD). Model-informed precision dosing (MIPD) offers a superior approach to maintaining target infliximab concentrations compared to emp...
Transforming Pediatric Rare Disease Drug Development: Enhancing Clinical Trials and Regulatory Evidence With Virtual Patients [0.03%]
儿科罕见病药物开发的变革：利用虚拟患者增强临床试验和监管证据
Fianne Sips,Marco Virgolin,Giuseppe Pasculli et al.
Fianne Sips et al.
Drug development in pediatric rare diseases is complicated by practical and ethical constraints on clinical trial design, stemming from small, highly heterogeneous, and vulnerable patient populations. Virtual patients (VPs) created with mac...
Moving From Point-Based Analysis to Systems-Based Modeling: Knowledge Integration to Address Antimicrobial Resistance [0.03%]
从基于积分的分析转向基于系统的建模：整合知识以应对抗菌素耐药性问题
Bhavatharini Arun,Gauri G Rao
Bhavatharini Arun
Optimizing antibiotic therapy requires a holistic bench-to-bedside approach with interdisciplinary collaboration between pharmacologists, clinicians, microbiologists, and computational scientists. Novel experimental models provide insights ...
Pharmacometric Model-Based Sample Size Allocation for a Region of Interest in a Multi-Regional Phase 2 Trial: A Case Study of an Anti-Psoriatic Drug [0.03%]
基于药代动力学模型的区域样本量分配在多地区II期临床试验中的一区间的案例研究：一种抗银屑病药物
Xiao Zhang,Yubo Xiao,Junyi Wu et al.
Xiao Zhang et al.
Phase 2 trials have historically focused on characterizing the dose-exposure-response relationship in relatively homogeneous patient populations before proceeding to confirmatory trials. However, with the rise of multi-regional Phase 2 tria...
PBPK Modeling to Predict Clinical Drug-Drug Interaction and Impact of Hepatic Impairment for an ADC With the Payload Auristatin F-Hydroxypropylamide [0.03%]
用于预测载荷为奥立斯坦F-羟丙胺的抗体药物偶联物临床药物相互作用及肝功能损害影响的PBPK建模研究
Niyanta Kumar,Vaishali Dixit,Howard Burt et al.
Niyanta Kumar et al.
Upifitamab rilsodotin-an antibody drug conjugate (ADC)-comprises a NaPi2b-targeted antibody conjugated to an auristatin-based payload (auristatin F-hydroxypropylamide [AF-HPA]). AF-HPA is metabolized by cytochrome P450 3A4 (CYP3A4) and, to ...