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Pharmacogenetics

By

Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Reviewed/Revised Jul 2022
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Topic Resources

Pharmacogenetics involves variations in drug response due to genetic makeup.

The activity of drug-metabolizing enzymes often varies widely among healthy people, making metabolism highly variable. Drug elimination rates vary up to 40-fold. Genetic factors and aging seem to account for most of these variations.

Pharmacogenetic variation (eg, in acetylation, hydrolysis, oxidation, or drug-metabolizing enzymes) can have clinical consequences (see table Examples of Pharmacogenetic Variations Examples of Pharmacogenetic Variations Examples of Pharmacogenetic Variations ). For example, if patients metabolize certain drugs rapidly, they may require higher, more frequent doses to achieve therapeutic concentrations; if patients metabolize certain drugs slowly, they may need lower, less frequent doses to avoid toxicity, particularly of drugs with a narrow margin of safety. For example, patients with inflammatory bowel disease who require azathioprine therapy are now routinely tested for thiopurine methyltransferase (TPMT) genotype to determine the most appropriate starting dose for drug therapy. Most genetic differences cannot be predicted before drug therapy, but for an increasing number of drugs (eg, carbamazepine, clopidogrel, warfarin), changes in effectiveness and risk of toxicity have been specifically associated with certain genetic variations. Also, many environmental and developmental factors can interact with each other and with genetic factors to affect drug response (see figure Genetic, environmental, and developmental factors that can interact Genetic, environmental, and developmental factors that can interact, causing variations in drug response among patients Genetic, environmental, and developmental factors that can interact, causing variations in drug response among patients ).

Table

Genetic, environmental, and developmental factors that can interact, causing variations in drug response among patients

Genetic, environmental, and developmental factors that can interact, causing variations in drug response among patients
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