Sampling from covariate distribution may not always be necessary in PK/PD simulations: illustrative examples with antibiotics [0.03%]
在PK / PD模拟中，不一定总是需要从协变量分布中采样：抗生素的示例说明
Feiyan Liu,Zeneng Cheng,Sanwang Li et al.
Feiyan Liu et al.
Pharmacokinetics (PK)/pharmacodynamics (PD) modeling and simulation is crucial for optimizing antimicrobial dosing. This study assessed covariate impact on PK variability and identified scenarios where fixing the covariate with median value...
The impact of misspecified covariate models on inclusion and omission bias when using fixed effects and full random effects models [0.03%]
当使用固定效应和完全随机效应模型时，协变量模型指定错误对包含偏差和遗漏偏差的影响
Joakim Nyberg,E Niclas Jonsson
Joakim Nyberg
Identification of covariates that can explain sources of variability among individuals in pharmacometric models is key, as it can lead to patient-subgrouping or patient-specific dosing strategies. Common recommendations propose to limit the...
Defining preclinical efficacy with the DNAPK inhibitor AZD7648 in combination with olaparib: a minimal systems pharmacokinetic-pharmacodynamic model [0.03%]
DNA-PK抑制剂AZD7648与奥拉帕利联合使用定义临床前疗效：最小系统药代动力学-药效学模型
Joost DeJongh,Elaine Cadogan,Michael Davies et al.
Joost DeJongh et al.
AZD7648 is a potent inhibitor of DNA-dependent protein kinase (DNA-PK), which is part of the non-homologous end-joining DNA repair pathway. When combined with the PARP inhibitor olaparib, AZD7648 shows robust combination activity in pre-cli...
Reliability of in vitro data for the mechanistic prediction of brain extracellular fluid pharmacokinetics of P-glycoprotein substrates in vivo; are we scaling correctly? [0.03%]
关于P-糖蛋白底物的体外数据可靠性的研究，该药物能否正确用于预测体内脑细胞外液药代动力学的机制性问题的研究；我们在进行比例缩放时是否准确？
Daan W van Valkengoed,Makoto Hirasawa,Vivi Rottschäfer et al.
Daan W van Valkengoed et al.
Plasma pharmacokinetic (PK) profiles often do not resemble the PK within the central nervous system (CNS) because of blood-brain-border (BBB) processes, like active efflux by P-glycoprotein (P-gp). Methods to predict CNS-PK are therefore de...
Quantifying natural amyloid plaque accumulation in the continuum of Alzheimer's disease using ADNI [0.03%]
使用ADNI量化阿尔茨海默病连续体中的天然淀粉样蛋白斑块积累程度
Marwa E Elhefnawy,Noel Patson,Samer Mouksassi et al.
Marwa E Elhefnawy et al.
Brain amyloid beta neuritic plaque accumulation is associated with an increased risk of progression to Alzheimer's disease (AD) [Pfeil, J., et al. in Neurobiol Aging 106: 119-129, 2021]. Several studies estimate rates of change in amyloid p...
Stronger together: a cross-SIG perspective on improving drug development [0.03%]
携手共进：关于改进药物开发的跨SIG视角
Luke Fostvedt,Jiawei Zhou,Anna G Kondic et al.
Luke Fostvedt et al.
A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment [0.03%]
用于alogliptin反应的生理基于定量系统药理学模型及在肾功能不全患者中的应用机制研究
Chaozhuang Shen,Haitang Xie,Xuehua Jiang et al.
Chaozhuang Shen et al.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In...
No QT interval prolongation effect of sepiapterin: a concentration-QTc analysis of pooled data from phase 1 and phase 3 studies in healthy volunteers and patients with phenylketonuria [0.03%]
孢吡品因无延长QT间期作用：健康人群和苯酮尿症患者一期及三期临床研究的汇总数据分析结果显示
Lan Gao,Yongjun Hu,Neil Smith et al.
Lan Gao et al.
Sepiapterin is an exogenously synthesized new chemical entity that is structurally equivalent to endogenous sepiapterin, a biological precursor of tetrahydrobiopterin (BH4), which is a cofactor for phenylalanine hydroxylase. Sepiapterin is ...
Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution? [0.03%]
P-糖蛋白介导的血脑屏障药物相互作用影响吗啡向脑内分布吗？
Berfin Gülave,Ariel Lesmana,Elizabeth Cm de Lange et al.
Berfin Gülave et al.
P-glycoprotein (P-gp) is a key efflux transporter and may be involved in drug-drug interactions (DDIs) at the blood-brain barrier (BBB), which could lead to changes in central nervous system (CNS) drug exposure. Morphine is a P-gp substrate...
Application of model-informed drug development (MIDD) for dose selection in regulatory submissions for drug approval in Japan [0.03%]
基于模型的药物研发（MIDD）在日本申报注册中的剂量选择应用
JPMA MIDD Task force;Tomohiro Sasaki,Takayuki Katsube,Seiichi Hayato et al.
JPMA MIDD Task force;Tomohiro Sasaki et al.
Model-informed drug development (MIDD) is an approach to improve the efficiency of drug development. To promote awareness and application of MIDD in Japan, the Data Science Expert Committee of the Drug Evaluation Committee in the Japan Phar...