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The rate at which healthy people metabolise drugs is variable. Although part of this variability is a consequence of environmental factors, including the influence of inducers and inhibitors, the main factor contributing to interindividual variability in metabolism is the underlying genetic basis of the drug‐metabolising enzymes. Although there is probably a genetic component in the control of most P450 enzymes, some enzymes (e.g. CYP2C19 and CYP2D6) actually show genetic polymorphism. This results in distinct subpopulations of poor and extensive metabolisers, where the poor metabolisers are deficient in that particular enzyme. There are a number of enzymes under polymorphic control and some clinically important examples are shown in Table 1.2. As with enzyme inhibition, genetic polymorphism is primarily a concern for drugs that have a narrow therapeutic index and that are metabolised largely by a single polymorphic enzyme. In such cases, the phenotype of the patient should be determined and lower doses of the drug used, or alternative therapy should be considered.

Table 1.2 Major enzymes displaying genetic polymorphism.