The AmpliChip CYP450 test: principles, challenges, and future clinical utility in digestive disease.
Understanding genetically encoded inherited differences in drug metabolism and targets (ie, receptors, transporters) offers the promise of minimizing adverse drug reactions and improving therapies. Among the enzymes involved in drug metabolism, the cytochromes P450 (CYP450) hold a central position. In fact, CYP450 are involved in the biotransformation of most drugs used in clinical practice. Recent advances in the development of DNA-based diagnostics, coupled with a better understanding of genetic polymorphisms in influencing pharmacologic responses, have provided the foundation for novel in vitro tests that may predict side effects and/or therapeutic responses. The AmpliChip CYP450 test was developed as a clinical test to evaluate an individual's metabolic capacity for certain drugs by identifying polymorphisms of 2 CYP450 enzymes (ie, CYP2D6 and CYP2D19). Even though the AmpliChip CYP450 has been approved by the US Food and Drug Administration, its practical clinical utility has not yet been determined, and there is a paucity of data related to gastrointestinal and liver diseases. An understanding of the principles and opportunities provided by this new category of diagnostic test is key before planning the necessary studies to evaluate the usefulness of AmpliChip CYP450 in gastroenterologic clinical practice.
Juran
Brian D
BD
Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Egan
Laurence J
LJ
Lazaridis
Konstantinos N
KN
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005765:Gastrointestinal Agents / Q000378:metabolism / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic
D005765:Gastrointestinal Agents; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; C105144:cytochrome P-450 CYP2D19 (marmoset)