Genetic Basis of Drug Metabolism

Margaret K. Ma, Michael H. Woo, Howard L. Mcleod


Am J Health Syst Pharm. 2002;59(21) 

In This Article


Major genetic polymorphisms that affect drug-metabolizing enzymes are summarized in Table 1 . The technology to identify SNPs is available, and databases that house these SNPs and gene sequence information are rapidly growing and readily accessible. In the past, pharmacogenetics has been used to explain clinically overt toxicity or the lack of efficacy in a subset of patients. As the field continues to develop, pharmacogenetics will play an important role in prospectively predicting a patient's drug activation and detoxification status, such that a therapeutic intervention can be made prior to drug administration without exposing the patient to drug toxicity or therapeutic failure. Further, recent evidence indicates that genotyping tests can more accurately predict a person's ability to metabolize certain drugs than an approach based solely on ethnic or geographic groups.[92,93] Although a genetic basis is preferable to less objective measures, such as skin color, currently there is no algorithm that can provide a comprehensive predictive surrogate for all drug-metabolizing-enzyme SNPs. Pharmacogenetics has thus far provided a drug-gene relationship to drug response and has contributed in learning how to administer certain drugs more effectively and safely. As functional consequences of polymorphisms within drug metabolizing enzymes become better understood and genotype analysis becomes less costly, pharmacogenetics may lead to the individualization of medication dosing and improved therapeutics.[60]