Advancing inclusive healthcare through PBPK modelling: predicting the impact of CYP genotypes and enzyme ontogenies on infant exposures of venlafaxine and its active metabolite O-desmethylvenlafaxine in lactation [0.03%]
通过PBPK建模推动包容性医疗保健：预测CYP基因型和酶发育对哺乳期间舍曲林及其活性代谢物去甲基舍曲林婴儿暴露的影响
Xian Pan,Karen Rowland Yeo
Xian Pan
About 15-20% of women experience postnatal depression and may seek advice about medication use whilst breastfeeding. Venlafaxine is a potent and selective neuronal serotonin-norepinephrine reuptake inhibitor indicated for treating major dep...
Niklas Hartung,Aleksandra Khatova
Niklas Hartung
Statistical modelling of covariate distributions allows to generate virtual populations or to impute missing values in a covariate dataset. Covariate distributions typically have non-Gaussian margins and show nonlinear correlation structure...
Imputation of missing clock times - application to procalcitonin concentration time course after birth [0.03%]
缺失钟时间的插补-应用于出生后降钙素原浓度的变化过程分析
Abigail J Bokor,Nick Holford,Jacqueline A Hannam
Abigail J Bokor
The time course of biomarkers (e.g., acute phase proteins) are typically described using days relative to events of interest, such as surgery or birth, without specifying the sample time. This limits their use as they may change rapidly dur...
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...