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Journal of Toxicology
Volume 2017 (2017), Article ID 1907952, 5 pages
https://doi.org/10.1155/2017/1907952
Review Article

Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing

1Durham VA Medical Center, Research & Development Service, Durham, NC 27705, USA
2Nephrology Division, Department of Internal Medicine, Duke University School of Medicine, Durham, NC 27705, USA
3Space Policy Institute, Elliott School of International Affairs, George Washington University, Washington, DC 20052, USA
4Department of Veterans Affairs Office of Research and Development, Washington, DC 20420, USA
5Departments of Otorhinolaryngology, Immunology, and Psychiatry, Baylor College of Medicine, Houston, TX 77030, USA

Correspondence should be addressed to Timothy G. Hammond and Holly H. Birdsall

Received 24 June 2017; Revised 27 July 2017; Accepted 7 August 2017; Published 10 September 2017

Academic Editor: Lucio Guido Costa

Copyright © 2017 Timothy G. Hammond and Holly H. Birdsall. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.