In vitro approaches to investigate cytochrome P450 activities: update on current status and their applicability. (September 2013)

• Record Type: Journal Article
• Authors: Ong, Chin Eng; Pan, Yan; Mak, Joon Wah; Ismail, Rusli
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 9:Number 9(2013:Sep.)
• Page Start: 1097
• Page End: 1113
• Publication Date: 2013-09
• Subjects: Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1517/17425255.2013.800482
• Languages: English
• ISSNs: 1742-5255

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Cytochromes P450 (CYPs) play a central role in the Phase I metabolism of drugs and other xenobiotics. It is estimated that CYPs can metabolize up to two-thirds of drugs present in humans. Over the past two decades, there have been numerous advances in <italic>in vitro</italic> methodologies to characterize drug metabolism and interaction involving CYPs.</p> <p> <bold> <italic>Areas covered:</italic> </bold> This review focuses on the use of <italic>in vitro</italic> methodologies to examine CYPs' role in drug metabolism and interaction. There is an emphasis on their current development, applicability, advantages and limitations as well as the use of <italic>in silico</italic> approaches in complementing and supporting <italic>in vitro</italic> data. The article also highlights the challenges in extrapolating <italic>in vitro</italic> data to <italic>in vivo</italic> situations.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> Advances in <italic>in vitro</italic> methodologies have been made such that data can be used for <italic>in vivo</italic> prediction with comfortable degree of confidence. Improved assay designs and analytical techniques have permitted development of miniaturized assay format and automated system with improved sensitivity and throughput capacity. High-quality experimental designs and scientifically rigorous assessment/validation protocols remain crucial in developing reliable and robust <italic>in vitro</italic> models. With continued progress made in the field, <italic>in vitro</italic> methodologies will continually be employed in evaluating CYP activities in pharmaceutical industries and laboratories.</p> </abstract>