Cytochrome P450 enzymes and genotype-guided drug therapy.
The cytochome P450 enzyme system is responsible for the metabolism of xenobiotics, including > 75% of commonly prescribed medications. Many of the cytochrome enzymes exhibit polymorphic genotypes, partly accounting for the variations observed in individual drug responses. Recent advances in the understanding of functional alleles of cytochrome P450 enzymes have changed the use of medications. Improvements in drug efficacy and the prevention of toxicity, as well as improvements in clinical drug dosing, have enhanced pharmacotherapy decisions in medical practice. In addition to personalizing medicine, the identification and quantification of genotypic differences in cytochrome P450 metabolism has the potential to facilitate population-based personalized medicine in countries without the resources to perform genotypic tests at the point of care. This review provides an update on the utility of genotype-guided therapy when treating breast cancer, malaria and coagulation disorders. Also discussed are advancements made in diagnostic tests for cytochrome genotypes and the need for future research in the area of diagnostic tests.
Roederer
Mary W
MW
University of North Carolina at Chapel Hill, UNC Eshelman School of Pharmacy, UNC Department of Family Medicine, 120 Mason Farm Road, CB#7361, Genetic Medicine Building, Chapel Hill, NC 27599-7361, USA. mroederer@unc.edu
D000655:Amodiaquine / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D057285:Precision Medicine; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015262:Xenobiotics / Q000378:metabolism
D000925:Anticoagulants; D000962:Antimalarials; D004965:Estrogen Antagonists; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D013629:Tamoxifen; D000655:Amodiaquine; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System