The major impact to date of polymorphic CYP expression has been on pre-clinical drug development.
The direct clinical impact of CYP polymorphisms on prediction of ADRs, however, has been limited mainly because published reports have been small and retrospective and their findings conflicting.
The Ampli Chip tests the DNA from a patient's leukocytes collected in a standard anti-coagulated blood sample for 29 polymorphisms and mutations for the CYP2D6 gene and 2 polymorphisms for the CYP2C19 gene.
CYP2D6 metabolizes about 25 % of all clinically used medications (e.g., antiarrhythmics, antidepressants, beta-blockers, dextromethorphan and morphine derivatives), while CYP2C19 metabolizes several important types of drugs including anti-epileptics and proton-pump inhibitors.
Individuals with a lack of functional activity in these enzymes should be treated with very low doses of drugs metabolized by the same enzyme to avoid excessive drug levels and thus toxic effects.
In recent years, research has been focused on gene coding for drug targets.
Until recently, investigations in this field have generally centered on gene coding for drug-metabolizing enzymes.
Inactivating mutations have been found in gene coding for enzymes belonging to the cytochrome P450 (CYP) system, which is important in the hepatic metabolism of many drugs.
However, the current understanding of the role of CYP2C9 in biotransformation of endogenous signaling molecules and in drug toxicity is relatively meager.Additionally, some tests may help provide information on how well a specific treatment may work for an individual.Cytochrome P450 enzymes are a group of enzymes that account for approximately 75 percent of drug metabolism in the human body.Moreover, the clinical- and cost-effectiveness of pre-prescription genotyping for CYP polymorphisms has not been established.More investigation is needed before prospective CYP genotyping can become routine clinical practice”.In the more frequent heterozygous carriers (genotype *1/*3), the clearances were between 40 and 75 %.In these cases in which individual dosages are derived from clinical drug effects, such as for oral anticoagulants, the pharmacogenetics-based dose adjustments showed a good correlation with the genotype-specific empirically derived doses.These investigators concluded that the concept of therapy based on genotyping for CYP polymorphisms has not been assessed in prospective, randomized, controlled studies in which one group is dosed according to genotype while another group is dosed in a usual manner.It is unlikely that CYP2C9 genotyping will become routine practice unless its clinical value is supported by such rigorous assessments.Genotyping for cytochrome P450 has been proposed for possible use in medical management of drug therapies including, but not limited to, antidepressants, antiepileptic, antipsychotics, barbituates, clopidogrel, opioid analgesics, proton pump inhibitors, tamoxifen or warfarin.Recent advances in molecular biology have improved the understanding of genetic factors underlying many ADRs.