In vitro measurements of metabolism for application in pharmacokinetic modeling

详细信息    查看全文

• 作者：John C. Lipscomb ; Torka S. Poet
• 关键词：Drug metabolism ; Genetic polymorphisms ; Interspecies extrapolation ; In vitro to in vivo extrapolation ; Physiologically based pharmacokinetic modeling ; Risk assessment
• 刊名：Pharmacology and Therapeutics
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：118
• 期：1
• 页码：82-103
• 全文大小：431 K

文摘

Human risk and exposure assessments require dosimetry information. Species-specific tissue dose response will be driven by physiological and biochemical processes. While metabolism and pharmacokinetic data are often not available in humans, they are much more available in laboratory animals; metabolic rate constants can be readily derived in vitro. The physiological differences between laboratory animals and humans are known. Biochemical processes, especially metabolism, can be measured in vitro and extrapolated to account for in vivo metabolism through clearance models or when linked to a physiologically based pharmacological (PBPK) model to describe the physiological processes, such as drug delivery to the metabolic organ. This review focuses on the different organ, cellular, and subcellular systems that can be used to measure in vitro metabolic rate constants and how those data are extrapolated to be used in biologically based modeling.