Drug Metabolism

Drug Metabolism encompasses enzymatic transformation of pharmaceutical compounds within the body, typically converting lipophilic drugs into more water-soluble metabolites facilitating elimination while potentially altering biological activity, generating active metabolites, or producing toxic species. These biotransformation reactions occur primarily in liver through Phase I oxidative, reductive, or hydrolytic processes catalysed predominantly by cytochrome P450 enzymes, followed by Phase II conjugation reactions attaching polar groups like glucuronic acid, sulphate, or glutathione to metabolites or parent drugs.

The pharmaceutical industry conducts extensive metabolism studies throughout preclinical and clinical development characterising biotransformation pathways, identifying metabolites, evaluating species differences, and assessing drug interaction potential. In vitro metabolism studies using liver microsomes, hepatocytes, or recombinant enzymes predict metabolic stability and identify responsible enzymes. Regulatory guidance requires safety assessment of major circulating metabolites. Pharmacogenomic considerations address genetic polymorphisms in metabolising enzymes affecting drug exposure and response across populations, informing dose adjustments or patient selection. Drug interaction studies evaluate whether investigational agents induce or inhibit metabolic enzymes potentially altering exposures of concomitant medications. Prodrug strategies intentionally design inactive compounds activated through metabolic conversion, improving delivery or reducing toxicity. As therapeutic molecules diversify beyond traditional small molecules to biologics and oligonucleotides with unique metabolic pathways, drug metabolism science continues evolving through advanced analytical capabilities and systems approaches.