Cytochrome P450 Assay Services

The Role of CYP450 Enzymes in Drug Metabolism

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases responsible for the oxidative metabolism of approximately 75% of marketed drugs. Expressed primarily in the liver, these enzymes catalyze Phase I biotransformation reactions that introduce polar functional groups into lipophilic substrates, facilitating their elimination from the body.

Seven CYP isoforms (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) account for the majority of drug metabolism, with CYP3A4 alone involved in the clearance of over 50% of therapeutics. Because CYP-mediated metabolism directly influences drug exposure, efficacy, and toxicity, understanding a compound’s interaction with these enzymes is essential for predicting pharmacokinetic behavior and mitigating drug-drug interaction (DDI) risks.

Why CYP450 Inhibition Assessment Matters
When a drug inhibits a CYP isoform, it can reduce the metabolic clearance of co-administered drugs metabolized by that enzyme, leading to elevated plasma concentrations and potential toxicity. This mechanism underlies the majority of clinically significant drug-drug interactions. FDA, EMA, and ICH M12 guidelines require in vitro assessment of CYP inhibition potential before clinical trials, making early-stage CYP profiling a regulatory necessity. Screening across major isoforms identifies metabolic liabilities while chemistry can still optimize around them.