We have discussed how an enzyme essential to the metabolic pathway of a particular drug can be deficient or defective due to hereditary factors (polymorphisms) and how these deficiencies can cause the drug to accumulate in the body (as seen in “poor metabolizers”) or have reduced efficacy (as seen in “ultrarapid metabolizers”).
Genetics can also indirectly influence the biotransformation of a drug. Genetic variation in the genes that control the synthesis of drug-receptor sites can affect the concentration of free drugs in the bloodstream that are available for metabolic processes. Genetic mutations in carrier proteins (such as albumin) can also affect circulating drug levels. The bioavailability of the drug can also be affected by variations in genes that control the synthesis of proteins available for protein binding.
