Biotransformation

Biotransformation designates the enzymatic conversion of pharmaceutical compounds within living organisms through Phase I reactions including oxidation, reduction, and hydrolysis followed by Phase II conjugation reactions, converting lipophilic drugs into more hydrophilic metabolites facilitating renal or biliary excretion while potentially generating active or toxic metabolite species.

The pharmaceutical industry characterises biotransformation pathways comprehensively throughout drug development to understand clearance mechanisms, identify metabolites requiring safety assessment, predict drug-drug interactions, and explain pharmacokinetic variability. In vitro studies using liver microsomes, hepatocytes, and recombinant enzymes identify responsible enzyme systems and reaction kinetics. In vivo mass balance studies quantify metabolite profiles in excreta. Reactive metabolite screening identifies potentially toxic biotransformation products. Species differences in biotransformation affect preclinical to human translation. Regulatory submissions include detailed biotransformation characterisation supporting clinical safety. As metabolic pathways become better understood and in vitro-in vivo extrapolation models improve, biotransformation characterisation continues supporting safe, efficient drug development.