期刊
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
卷 6, 期 2, 页码 171-187出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425250903436486
关键词
absorption; ADME; BBB; BCS; bioavailability; Caco-2 ISIVIVC; PAMPA; permeability; P-gp; transporter
资金
- Novartis Institutes
Importance of the field. Adequate permeability is essential for good oral absorption and proper interpretation of pharmacokinetic and pharmacological data. Permeability-limiting absorption and distribution, however, are complex phenomena involving multiple mechanisms and organs ranging from gastro-intestine, liver, kidney to BBB, while the options for pharmaceutical improvement of permeability are quite limited. Areas covered in this review. in this article, the comprehensive in silica, in vitro and in vivolex vivolin situ tools to assess permeability are reviewed, alongside their advantages and limitations. Several key points relating to the in vivo predictive impact of in vitro permeability tools and the caveats when dealing with challenging discovery compounds were also addressed, using drug discovery cases and statistics in Novartis. What the reader will gain: The integrated strategy to properly utilize existing permeability tools for mitigating the permeability-related absorption or safety risks at the different stages of drug discovery and development processes is presented. Take home message: It is critical to utilize the comprehensive in silica, in vitro and in vivolex vivo tools to dial out permeability issues in early drug discovery, ensuring the right questions to be addressed using the right tools at the right time.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据