视频 | 整合转运体动力学到生理药动学模型中
内容概要
转运体将影响药物的吸收、处置、清除、药物相互作用DDI,其重要性在近几年引起广泛的重视,在药物处置领域转运体的作用已取得了重大进展。
缺乏转运体在不同器官的表达水平的完全数据,同时我们得到的药物特异性表达数据往往都是体外数据,这通常是我们无法准确预测转运体参与药物处置的体内暴露量的主要原因。
最近,有大量的文章是关于该领域的,主要关注在不同物种,不同器官上转运体mTNA和/或蛋白水平的定量研究。
本讲座将阐述对于化合物来说,转运体介导的分泌及代谢酶介导的代谢的协同作用是非常重要的,以它们是如何影响体外体内外推IVIVE的成功率。
最后,Lukacova博士将讲解一个案例: PBPK模型的搭建与开发,随后在儿童人群中预测其PK行为,该化合物主要是通过转运体介导的分泌进行消除的。
The importance of transporter effects on drug absorption, disposition, clearance, and drug-drug interactions has gained considerable attention over the past few years. Significant progress has been made in identifying the gaps in knowledge about the role of transporters in drug disposition.
Lack of data on absolute expression levels of transporters in various tissues, as well as our ability to relate those expressions to drug-specific in vitro data, are frequently indicated as primary reasons behind our inability to reliably predict the in vivo exposure of drugs whose disposition is dependent on interactions with transporters.
Research investments in this area have resulted in a large number of recent publications focused on quantifying the transporter mRNA and/or protein levels in various tissues in different species.
One of the previous webinars in this series discussed transporters affecting drug absorption. This webinar will focus more on transporters involved in drug distribution and elimination.
A brief summary of current information on transporter expression levels will be followed by a description of options for including transporters in the GastroPlus™ PBPK model.
The importance of interplay between transporter-mediated secretion and metabolism of a compound, and how it may affect the successful in vitro-in vivo extrapolation (IVIVE) of metabolic clearance, will be discussed.
Finally, we will present an example of PBPK model development and subsequent prediction of pharmacokinetics in a pediatric population for a compound eliminated primarily via transporter-mediated secretion.
讲解人
Viera Lukacova, Ph.D.
Team Leader - Simulation Technologies
Simulations Plus, Inc.
课程视频