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Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing
Joint Authors
Birdsall, Holly H.
Hammond, Timothy G.
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-5, 5 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-09-10
Country of Publication
Egypt
No. of Pages
5
Main Subjects
Abstract EN
Cytochrome 2B6 (CYP2B6) has substantial clinical effects on morbidity and mortality and its effects on drug metabolism should be part of hepatotoxicity screening.
Examples of CYP2B6’s impacts include its linkage to mortality during cyclophosphamide therapy and its role in determining hepatotoxicity and CNS toxicity during efavirenz therapy for HIV infection.
CYP2B6 is key to metabolism of many common drugs from opioids to antidepressants, anesthetics, and anticonvulsants.
But CYP2B6 has been extremely difficult to express in cell culture, and as a result, it has been largely deemphasized in preclinical toxicity studies.
It has now been shown that CYP2B6 expression can be supported for extended periods of time using suspension culture techniques that exert physiological levels of shear.
New understanding of CYP2B6 has identified five clinically significant genetic polymorphisms that have a high incidence in many populations and that convey a substantial dynamic range of activity.
We propose that, with the use of culture devices exerting physiological shear levels, CYP2B6 dependent drug testing, including definition of polymorphisms and application of specific inhibitors, should be a standard part of preclinical absorption, distribution, metabolism, and excretion (ADME) testing.
American Psychological Association (APA)
Hammond, Timothy G.& Birdsall, Holly H.. 2017. Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing. Journal of Toxicology،Vol. 2017, no. 2017, pp.1-5.
https://search.emarefa.net/detail/BIM-1187890
Modern Language Association (MLA)
Hammond, Timothy G.& Birdsall, Holly H.. Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing. Journal of Toxicology No. 2017 (2017), pp.1-5.
https://search.emarefa.net/detail/BIM-1187890
American Medical Association (AMA)
Hammond, Timothy G.& Birdsall, Holly H.. Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing. Journal of Toxicology. 2017. Vol. 2017, no. 2017, pp.1-5.
https://search.emarefa.net/detail/BIM-1187890
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1187890