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

Publication ,  Journal Article
Hammond, TG; Birdsall, HH
Published in: J Toxicol
2017

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.

Duke Scholars

Published In

J Toxicol

DOI

ISSN

1687-8191

Publication Date

2017

Volume

2017

Start / End Page

1907952

Location

Egypt

Related Subject Headings

  • 4104 Environmental management
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0502 Environmental Science and Management
  • 0304 Medicinal and Biomolecular Chemistry
 

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Hammond, T. G., & Birdsall, H. H. (2017). Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing. J Toxicol, 2017, 1907952. https://doi.org/10.1155/2017/1907952
Hammond, Timothy G., and Holly H. Birdsall. “Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing.J Toxicol 2017 (2017): 1907952. https://doi.org/10.1155/2017/1907952.
Hammond, Timothy G., and Holly H. Birdsall. “Hepatocyte CYP2B6 Can Be Expressed in Cell Culture Systems by Exerting Physiological Levels of Shear: Implications for ADME Testing.J Toxicol, vol. 2017, 2017, p. 1907952. Pubmed, doi:10.1155/2017/1907952.
Journal cover image

Published In

J Toxicol

DOI

ISSN

1687-8191

Publication Date

2017

Volume

2017

Start / End Page

1907952

Location

Egypt

Related Subject Headings

  • 4104 Environmental management
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0502 Environmental Science and Management
  • 0304 Medicinal and Biomolecular Chemistry