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The genetic basis of variability in drug responses
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Journal Article
The genetic basis of variability in drug responses
2002
Overview
Key Points
Variability in response to therapy is an expected feature of most drug treatments.
Pharmacokinetic variability arises because of variable delivery of a dose of a drug to target sites; that is, variability in the relationship between drug dose and plasma and tissue drug concentrations.
Pharmacodynamic variability arises because of variability in the relationship between drug concentration and effect.
In either case, variants in individual genes that mediate drug concentrations or their effects are increasingly being recognized as sources of variable drug action — 'pharmacogenetics'.
The sequencing of the human genome now raises the possibility of identifying many genetic variants, each contributing to overall variability in drug action: this is one definition of 'pharmacogenomics.'
We propose an algorithm for use in the pharmacogenomic profiling of adverse responses to drug action.
Although the vision of choosing 'personalized medicines' based on individual genetic profiles is an appealing one, substantial obstacles will need to be overcome if this is to become practical: these include logistic, analytical, biostatistical and ethical issues.
It is almost axiomatic that patients vary widely in their beneficial responses to drug therapy, and serious and apparently unpredictable adverse drug reactions continue to be a major public health problem. Here, we discuss the concept that genetic variants might determine much of this variability in drug response, and propose an algorithm to enable further evaluation of the benefits and pitfalls of this enticing possibility.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
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