The liver is responsible for metabolizing the majority of drugs. Metabolism occurs via enzymes that are responsible for increasing the water-solubility of drugs, so they can be excreted by the kidneys. The hepatic drug-metabolizing enzymes catalyze hydroxylation, oxidation, reduction, and conjugation reactions. These enzymatic processes are grouped into phase I and phase II reactions.

Phase I reactions are catalyzed by the cytochrome p450 superfamily or CYPs. CYPs facilitate reactions that enhance the water-solubility of drugs. The activity of CYPs is influenced by genetics and environmental factors such as diet and age.

Genetic polymorphisms that affect the CYP enzymes are seen in 5-20 percent of the population.[1,2] These functional polymorphisms can lead to either enhanced or diminished activity of the affected enzyme, and may explain some of the individual hypersensitivity reactions to specific drugs. The pattern of inheritance for CYP2D6 is autosomal recessive.[3]

The simultaneous use of two or more drugs affects drug metabolism by CYPs. A CYP substrate may either inhibit or enhance another substrate's metabolism.[4] Approximately 25% of drugs in clinical use are metabolized by the CYP2D6 superfamily.

Following phase I metabolism, most drugs need to undergo additional reactions to become more water soluble to become excreted. Phase II reactions result in the formation of excretable, nontoxic substances.[5,6] Similar to phase I enzymes, genetic polymorphisms in the phase II enzymes can also lead to either decreased or increased activity. This can be seen in the glutathione transferase enzyme family and in certain chemical carcinogens that can cause liver damage if not metabolized properly.[7]