視頻 | 整合轉運體動力學到生理藥動學模型中

缺乏轉運體在不同器官的表達水平的完全數據，同時我們得到的藥物特異性表達數據往往都是體外數據，這通常是我們無法準確預測轉運體參與藥物處置的體內暴露量的主要原因。

最近，有大量的文章是關于該領域的，主要關注在不同物種，不同器官上轉運體mTNA和/或蛋白水平的定量研究。

本講座將闡述對于化合物來說，轉運體介導的分泌及代謝酶介導的代謝的協同作用是非常重要的，以它們是如何影響體外體內外推IVIVE的成功率。

最后，Lukacova博士將講解一個案例: PBPK模型的搭建與開發，隨后在兒童人群中預測其PK行為，該化合物主要是通過轉運體介導的分泌進行消除的。

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. 

講解人