Induction of CYP2B6 and CYP3A4 Expression by 1-Aminobenzotriazole (ABT) in Human Hepatocytes

Author(s): Kyunghee Yang , Kwi Hye Koh , Hyunyoung Jeong .

Journal Name: Drug Metabolism Letters

Volume 4 , Issue 3 , 2010

Become EABM
Become Reviewer


1-Aminobenzotriazole (ABT) has been widely used in drug development process as an irreversible inhibitor of CYP enzymes. One potential use of ABT is to potentiate pharmacological effects of rapidly-metabolized drugs on CYP expression by inhibiting their metabolism; however, ABTs own effects on CYP expression have been unknown. In this study, we show that ABT up-regulates expression of CYP2B6 and CYP3A4 potentially by activating nuclear receptor CAR. In freshly isolated human hepatocytes, ABT increased mRNA expression of CYP2B6 and CYP3A4 in a concentration- dependent manner. ABT also modulated CYP-inducing actions of CITCO and rifampin, the known inducers of CYP2B6 and CYP3A4. Results from luciferase reporter assays confirmed that ABT increases CYP2B6 promoter activity in CAR-expressing HepG2 cells. These results suggest that the use of ABT as a potentiator of pharmacological effects of rapidly-metabolized drugs is limited due to its own pharmacological actions on CYP expression as a CAR activator.

Keywords: 1-Aminobenzotriazole, CAR, CYP2B6, CYP3A4, CYP induction

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2010
Page: [129 - 133]
Pages: 5
DOI: 10.2174/187231210791698410
Price: $58

Article Metrics

PDF: 8