Cytochrome P450 Enzymes: A Review on Drug Metabolizing Enzyme Inhibition Studies in Drug Discovery and Development

Abstract

Assessment of drug candidate's potential to inhibit cytochrome P450 (CYP) enzymes remains crucial in pharmaceutical drug discovery and development. Both direct and time-dependent inhibition of drug metabolizing CYP enzymes by the concomitant administered drug is the leading cause of drug–drug interactions (DDIs), resulting in the increased toxicity of the victim drug. In this context, pharmaceutical companies have grown increasingly diligent in limiting CYP inhibition liabilities of drug candidates in the early stages and examining risk assessments throughout the drug development process. This review discusses different strategies and decision-making processes for assessing the drug–drug interaction risks by enzyme inhibition and lays particular emphasis on in vitro study designs and interpretation of CYP inhibition data in a stage-appropriate context.

Graphical abstract

Keywords:

• cytochrome P450 enzymes
• direct enzyme inhibition
• drug–drug interactions
• drug discovery and development
• time-dependent enzyme inhibition

Financial & competing interests disclosure

The authors are grateful to the Department of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Government of India, New Delhi, for the award of the NIPER fellowship. The manuscript bears the NIPER-Hyderabad communication number NIPER-H/2021/175. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.