Characterization of the metabolic contributions of cytochrome P450 isoforms to bicyclol using the relative activity factor method

Abstract

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6–90.3% and 9.2–9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug–drug interactions or toxicity in clinical applications of bicyclol.

Keywords:

• Hepatoprotectant
• relative activity factor
• drug-metabolizing enzyme
• enzyme contribution
• drug–drug interaction

Disclosure statement

These authors have declared no relevant financial or non-financial interests.

Data availability statement

Data and materials supporting the findings of the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

Research funded by National Key Research and Development Program of China (2022YFA0806400).