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Pharmacogenomics is a rapidly growing area of knowledge regarding the genetic variations that influence drug metabolism and drug effects. Most of the research in this field to date has involved phase I or phase II drug metabolism and drug transport. Application of genomic analysis of individual patients to selection of specific drugs and drug dosage is under investigation.
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The inheritance of genetic information via the double DNA helix is now well-understood. The decoding of the human genome and of many animal and plant genomes has opened a field of research into the molecular basis of variations between individuals and among populations. The identification of the specific genes (or groups of genes) that affect drug responses is still incomplete, but knowledge about a small number of these genes of pharmacologic significance has suggested the possibility that “personalized medicine” is possible and may become practical in the near future.
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Personalized medicine denotes clinical treatment that takes into account the genetic factors that contribute to disease and the pharmacogenomic factors that influence the response to drug treatment in specific individuals. Intense academic and commercial research is currently directed at discovering these factors. Research is also directed at developing accurate and inexpensive tests for pharmacogenetic factors in individual patients.
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As noted in Chapter 4, important genetic variations in drug metabolism exist between individuals. Furthermore, genetic diseases alter many functions that are drug targets. The identification of specific genes that control the expression of the molecules involved and the variants (polymorphisms) of those genes has become the subject of intense research over the last 10–20 years. At present, much data are available regarding the variants of the genes for some phase I and phase II enzymes and some drug transporters. Examples of these genetic determinants of drug metabolism and transport are the subject of this chapter.
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