Pharmacogenomics of Drug Metabolism
The convergence of pharmacogenetics and human genomics has resulted
in the field of pharmacogenomics, a term used to
describe the influence of DNA-sequence variation on the effect of a drug. The field
of pharmacogenomics began with a focus on drug metabolism but has been extended to
include the full spectrum of drug disposition, including absorption, transporters,
excretion, drug targets, and signal transduction. With the completion of the Human
Genome Project, the time is rapidly approaching when the sequences of virtually all
genes encoding enzymes that catalyze phase 1 and phase 2 reactions will be known.
More than 1.4 million single nucleotide polymorphisms were identified in the initial
screening of the human genome, with more than 60,000 in the coding region for genes.
Some of these single-nucleotide polymorphisms (SNPs) have already been associated
with substantial changes in the metabolism or effects of medications, and some are
being used to predict clinical response. The potential exists for pharmacogenomics
to yield a powerful set of molecular diagnostic tools with which clinicians can select
medications and drug doses for individual patients.
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