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

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

Volume: 4 Issue: 3

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Yang Kyunghee, Hye Koh Kwi and Jeong Hyunyoung, Induction of CYP2B6 and CYP3A4 Expression by 1-Aminobenzotriazole (ABT) in Human Hepatocytes, Drug Metabolism Letters 2010; 4 (3) . https://dx.doi.org/10.2174/187231210791698410