Applications of AmpliChip CYP450.

Abstract

Pharmacogenetics has assumed increasing importance with the developing concepts of personalized medicine. There is a need to determine the metabolic status of an individual when using drugs, the actions of which are influenced by drug-metabolizing enzymes. Cytochrome P450 (CYP) and its variants, particularly CYP2D6 and CYP2C19, play a role in the metabolism of approximately 25% of all prescription drugs. This review covers the role of the CYP system not only in the metabolism of drugs but also in the pathophysiology of disease. Various technologies for the assessment of CYP status are described, with the focus on AmpliChip CYP450 (Roche Molecular Diagnostics, Alameda, CA, USA), the first approved microarray molecular diagnostic test for the analysis of 29 polymorphisms and mutations of the CYP2D6 gene, and two polymorphisms of the CYP2C19 gene. It combines Roche's PCR technology with the GeneChip microarray system (Affymetrix, Santa Clara, CA, USA). Examples of numerous drugs that are metabolized by the CYP system are listed, and categories of antidepressants, antipsychotics, immunosuppressive and anticancer drugs are described to illustrate the role of testing for CYP polymorphisms in the therapeutic use of these drugs. CYP testing has applications in toxicology and absorption, distribution, metabolism and excretion (ADME) profiling as a guide to drug development. AmpliChip CYP450 may be used in conjunction with pharmacotherapy to guide decision making about selection of drugs and dosage. The test is not a solitary tool to determine optimum drug dosage, but is meant for use along with clinical evaluation and other methods for the selection of the treatment that is best suited for an individual patient. AmpliChip CYP450 is the first DNA microarray test to be cleared by the US FDA, and its clearance paves the way for similar microarray-based diagnostic tests to be developed in the future. This will facilitate the development of personalized medicine.