Pharmacogenomics and individualized drug therapy.
Pharmacogenetics deals with inherited differences in the response to drugs. The best-recognized examples are genetic polymorphisms of drug-metabolizing enzymes, which affect about 30% of all drugs. Loss of function of thiopurine S-methyltransferase (TPMT) results in severe and life-threatening hematopoietic toxicity if patients receive standard doses of mercaptopurine and azathioprine. Gene duplication of cytochrome P4502D6 (CYP2D6), which metabolizes many antidepressants, has been identified as a mechanism of poor response in the treatment of depression. There is also a growing list of genetic polymorphisms in drug targets that have been shown to influence drug response. A major limitation that has heretofore moderated the use of pharmacogenetic testing in the clinical setting is the lack of prospective clinical trials demonstrating that such testing can improve the benefit/risk ratio of drug therapy.
Eichelbaum
Michel
M
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, D-70376 Stuttgart, Germany. michel.eichelbaum@ikp-stuttgart.de
Ingelman-Sundberg
Magnus
M
Evans
William E
WE
D001711:Biotransformation / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics; D000099148:UGT1A1 Enzyme
D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D008780:Methyltransferases; D018343:Receptors, Adrenergic, beta-2; D015222:Sodium Channels; D000099148:UGT1A1 Enzyme; C022745:thiopurine methyltransferase