Metabolizers

Metabolizers is a term used in pharmacology and pharmacogenetics to describe individuals' efficiency in metabolizing drugs and other xenobiotics. Most drug metabolism occurs in the liver through enzymes, particularly the cytochrome P450 (CYP) family. Based on enzyme activity, people are commonly categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), or ultra-rapid metabolizers (URM). These categories reflect the rate at which a drug is converted to active or inactive forms, affecting drug exposure and response.

Genetic variation in drug‑metabolizing enzymes underlies these categories. Polymorphisms in genes such as CYP2D6, CYP2C19, and CYP3A4 can reduce, abolish, duplicate, or enhance enzyme activity. For CYP2D6, individuals may lack functional copies (PM) or have multiple copies (URM). Testing can be genotyping for known alleles or phenotyping with a probe drug to estimate metabolic capacity. Clinically, pharmacogenetic information informs dosing, drug choice, or avoidance of certain drugs; for example, PMs may experience toxicity with standard doses of prodrugs requiring activation, whereas URMs may have insufficient drug levels with standard doses.

Metabolic status also varies with non-genetic factors, including age, liver disease, pregnancy, diet, and concomitant medications that inhibit or induce enzyme activity. Environmental factors and the microbiome may contribute to metabolism. Because metabolic rate can differ by drug and context, genotype alone does not always predict response. Testing is not routinely performed for all medications; it is most relevant for drugs with narrow therapeutic windows or well-established pharmacogenetic guidelines. Ethnic groups show different frequencies of metabolizer phenotypes, which has implications for population-based prescribing.