DMET Plus Premier Pack

Standardize Your Drug Metabolism & Toxicology Studies

The DMET™ Plus Premier Pack, which includes arrays, reagents, and analysis software, is the most comprehensive, cost-effective product containing known pharmacogenetic markers for drug metabolism studies. The DMET Plus Premier Pack standardizes drug metabolism studies and enables faster discovery and measurement of genetic variation associated with drug response compared to traditional methods.

The DMET™ Plus Panel features markers in all FDA-validated genes and covers more than 90 percent of the current ADME Core markers as defined by the PharmaADME group. Affymetrix developed this drug metabolism panel in collaboration with key opinion leaders from both industry and academia.

Key Benefits

• Standardizes ADME content
• Delivers the most biologically relevant, high-value data
• Streamlines workflow for cost effectiveness

Key Features

• 1,936 drug metabolism markers in ~230 genes
• Markers in all FDA-validated genes
• More than 90 percent of the ADME Core markers as defined by the PharmaADME group
• Translation table for automated star allele analysis

The DMET Plus Panel provides coverage of a wide range of genetic variations, including common and rare SNPs, insertions, deletions, tri-alleles, and copy number——many of which are not assayed by conventional SNP methods. Unlike other SNP detection methods which interrogate markers with an average minor allele frequency (MAF) of approximately 20 percent, the ADME Core markers in the DMET Plus Panel have allelic frequencies below 9 percent, although more common genetic variants are also present.

With the DMET Plus Premier Pack, you can:

• Discover new biomarker associations
• Determine drug responders versus non-responders
• Identify populations at risk for adverse events
• Optimize drug dosing
• Analyze drug response outliers
• Selectively recruit for clinical trials
• Differentiate new drug to top-line therapy
• Investigate method of action

The DMET Plus Premier Pack is compatible with the GeneChip® Scanner 3000 7G System, GeneChip® Scanner 3000 7G Whole-Genome Association System, and GeneChip® Scanner 3000 Targeted Genotyping System.

Proven

The high-value, unique content of the DMET Plus Panel enables the identification of significant, new biomarker associations. Warfarin, which is prescribed to prevent heart attacks and strokes, is one of the top 10 drugs known to cause severe adverse events, including drug-related death. In a recent warfarin study using the DMET Panel, researchers discovered a new variant in CYP4F2 (a drug metabolizing enzyme) which explained 8 percent of dosing variability in select patient populations (Caldwell, et al., Blood, 2008). This new biomarker is being tested in a Phase III prospective trial. The discovery was a direct result of our drug metabolism panel-based approach and was missed by other pharmacogenetic approaches.

Fast

With the DMET Plus Premier Pack, you can query 1,936 known ADME markers simultaneously rather than having to run multiple, consecutive experiments. In addition, the translation table included in DMET™ Console Software automatically translates SNP and non-SNP genotyping results into standardized star allele nomenclature (i.e., CYP2D6*3 or CYP2C19*2), so you can easily integrate your data into existing workflows. This process is completed in minutes rather than days, saving you time and money.

Flexible

DMET Console Software features easy-to-use controls for marker content to ensure that the genetic markers reported in clinical studies are consented to, and compliant with, informed consent and other Institutional Review Board (IRB) requirements. The software also enables single-sample processing by relying on pre-set and analytically validated cluster boundaries for each DMET Plus variant. This means no minimum on the number of samples that can be run at one time, and that each sample's genotyping result is completely independent. This approach offers a high degree of flexibility when it comes to sample analysis and also maintains the integrity of individual sample results.

Precise

The DMET Plus Premier Pack contains synthetic plasmid DNA controls for all verified markers, so you can be confident in your genotyping results.

Timely

The DMET Plus Premier Pack is available for use in your lab or through qualified service providers. Please contact your local account manager for more information.

Recent Testimonials

"The DMET Panel has allowed us to better delineate the stable therapeutic dose of warfarin for our patients at the initiation of therapy, where risk of complications from the drug are at their highest. Our hope is that these studies will enable us to reduce the overall complications of warfarin therapy by a better prediction of stable therapeutic dose."

--Michael Caldwell, M.D., Ph.D., Director, Wound Healing Program, Marshfield Clinic

"The DMET Panel allowed us to characterize the pharmacogenetics of the chemotherapeutic agents docetaxel and thalidomide in patients treated for prostate cancer in a Phase II clinical trial, demonstrating that the DMET Panel can readily be incorporated into cancer clinical trials. The breadth and depth of the DMET Panel provides a unique approach to determining relevance of genetic variations across a drug's metabolic pathway. We plan to continue our work with the DMET Panel by characterizing the NCI60 cell lines. These cancer cell lines are used throughout the world to understand the molecular biology of cancer as well as cellular response to chemotherapy. More than 100,000 potential anticancer drugs have been tested against these cells lines by the National Cancer Institute. We hope to better understand the pharmacogenetics of literally hundreds of anticancer agents through the use of the DMET Panel."

--John Deeken, M.D., Lombardi Comprehensive Cancer Center, Georgetown University

Publications

Below is a selected list of publications utilizing DMET technology for pharmacogenomic and toxicity studies. To see a complete list, you may also conduct your own search.

• Daly, T. M., et al. Multiplex assay for comprehensive genotyping of genes involved in drug metabolism, excretion, and transport. Clinical Chemistry (2007). Pubmed
• Caldwell, M. D., et al. CYP4F2 genetic variant alters required warfarin dose. Blood (2008). Pubmed
• Dumaual, C., et al. Comprehensive assessment of metabolic enzyme and transporter genes using the Affymetrix® Targeted Genotyping System. Pharmacogenomics (2007). Pubmed
• Deeken, J. F., et al. A pharmacogenetic study of docetaxel and thalidomide in patients with androgen-independent prostate cancer (AIPC) using targeted human DMET genotyping platform. Abstract #3580, ASCO Meeting (2007).
• Robarge, J. D., et al. The Star-Allele Nomenclature: Retooling for Translational Genomics. Nature (2007).
• Frueh, F. W., et al. Pharmacogenomic Biomarker Information in Drug Labels Approved by the United States Food and Drug Administration: Prevalence of Related Drug Use. Pharmacotherapy (2008).
• Mega, J. L., et al. Cytochrome P-450 Polymorphisms and Response to Clopidogrel. New England Journal of Medicine 360(4), 354-62 (2009).
• Varenhorst, C., et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease. European Heart Journal 30(14), 1744-52, (2009).
• Nebert, D. W. Polymorphisms in Drug-Metabolizing Enzymes: What Is Their Clinical Relevance and Why Do They Exist? American Journal of Human Genetics (1997).
• Man, M., et al. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. Journal of Clinical Pharmacology 50(8) 929-40 (2010).

Additional Information

Please contact us for a complete list of authorized service providers.

For Research Use Only. Not for use in diagnostic procedures.