Molecular genetics of cytochrome P450 enzymes (CYPs) in relation to the drug development and drug treatment are reviewed. CYPs play a key role in the metabolism of various drugs. The capacity of CYPs varies from one person to another, leading to variable rates of drug metabolism. This variability is mainly due to the genetic polymorphism of CYPs. A number of different functional alleles of different CYPs have been identified. CYP2D6, CYP2C19 and CYP2C9 are the three most well studied and best characterized. On the other hand, CYP3A4 is the most important isoform of CYPs which metabolizes more than half of substrate drugs of CYPs. Although CYP3A4 is known to show wide inter-individual variation, it has not been attributed to genetic factor but to rather induction and inhibition of this enzyme. However, up to now the existence of 12 mutant alleles have been reported for this enzyme and variable capacity of CYP3A4 is now recognized to be explainable in part by the genetic factors. In this article, CYP2D6, CYP2C19, CYP2C9 and CYP3A4 will be dealt with in some detail but other CYPs will be covered in outline.
