ABSTRACT
This chapter highlights current pharmacogenetic knowledge on
important human drug-metabolizing cytochrome P450s (CYPs) to
understand the large interindividual variability in drug clearance
and responses in clinical practice. The human CYP superfamily
contains 57 functional genes and 58 pseudogenes, with members
of families 1, 2, and 3 playing an important role in the metabolism
of therapeutic drugs, other xenobiotics, and some endogenous
compounds. Polymorphisms in the CYP family may have had the
most impact on the fate of therapeutic drugs. CYP2D6, 2C19, and 2C9 polymorphisms account for the most frequent variations in phase I metabolism of drugs since almost 80% of drugs in use today
are metabolized by these enzymes. Extensive polymorphism also
occurs in other CYP genes such as CYP1A2, 2A6, 2A13, 2C8, 3A4, and
3A5. The distribution of the common variant alleles of CYP genes varies among different ethnic populations. Pharmacogenetics has
the potential to achieve optimal quality use of medicines and to
improve the efficacy and safety of both prospective and currently
available drugs. Further studies are warranted to explore the
gene-dose, gene-concentration, and gene-response relationships
for these important drug-metabolizing CYPs.
