More than 300 genes are known to be involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs. These include key transporters and drug metabolism genes such as the cytochrome P450s and UDP-glucuronosyltransferases. Genetic variation in ADME genes impacts the effectiveness, side effects, and ideal dosage of drugs in different patients, and has become an important aspect of precision medicine, patient stratification, and treatment planning. Scientists at Frontage have developed methods to rapidly genotype ADME genes in patients and predict drug metabolism and response to support our clients in their research and clinical trials.  

The genomics team at Frontage has expertise in variant detection and genotyping a variety of methods. Genomic DNA can be examined using next-generation sequencing NGS technology with our custom pharmacogenomics panel to simultaneously determine the phenotypes of over 300 genes involved in drug metabolism and response. Alternatively, PCR-based approaches allow for a more focused approach to genotype specific SNPs in a smaller subset of genes.  

The genomics team at Frontage has expertise in SNP genotyping using qPCR, including extensive experience in custom assay design and assay optimization.

The pharmacogenomics (PGx) platform offered at Frontage makes use of NGS technology to simultaneously examine hundreds of genes involved in drug metabolism and response and predict the metabolic rate of processing for more than 100 different pharmaceuticals belonging to various drug classes.  Frontage’s NGS PGx platform allows for more comprehensive, accurate, and cost-effective genotyping for multiple genes.  

Frontage has developed an NGS-based hybridization capture panel that targets the coding regions of 364 genes involved in ADME, including the most well-studied transporters and drug metabolism genes. Frontage’s PGx platform enables the calling of star alleles based on thousands of polymorphic sites spread across the genes included in the panel. The ability to generate star allele calls based on data from multiple polymorphic sites per gene enables detection of a greater repertoire of alleles across a larger number of ADME-related genes compared to other technologies, providing more accurate predictions of drug metabolism.

The end-to-end PGx services offered at Frontage include genotype summaries and drug metabolism predictions and recommendations as part of a comprehensive report that presents key information in an easily accessible format.

Combining Frontage’s NGS-based PGx platform with the Pharmacogenomics Clinical Annotation Tool (PharmCAT) software enables the generation of drug metab

Key Drug Metabolism and Transporter Genes included in the PGx Report

GeneGene Description 
No. Alleles called in PharmCat v. 2.1 
ABCG2 ATP binding cassette subfamily G member 2 (Junior blood group) 
CACNA1S Calcium voltage-gated channel subunit alpha1S 
CFTR Cystic fibrosis transmembrane conductance regulator 40 
CYP2B6 Cytochrome P450 2B6 35 
CYP2C19 Cytochrome P450 2C19 34 
CYP2C9 Cytochrome P450 2C9 85 
CYP2D6 Cytochrome P450 2D6 149* 
CYP3A4 Cytochrome P450 3A4 35 
CYP3A5 Cytochrome P450 3A5 
CYP4F2 Cytochrome P450 4F2 
DPYD Dihydropyrimidine dehydrogenase 83 
G6PD Glucose-6-phosphate dehydrogenase 185 
IFNL3 Interferon Lambda 3 
NUDT15 Nudix hydrolase 15 20 
RYR1 Ryanodine receptor 1 49 
SLCO1B1 Solute carrier organic anion transporter family member 1B1 42 
TPMT Thiopurine methyltransferase 46 
UGT1A1 UDP glucuronosyltransferase 1A1 
VKORC1 Vitamin K epoxide reductase complex subunit I 

Frontage’s NGS PGx platform is validated for clinical use under CLIA/CAP, and was found to perform with 100% specificity, selectivity, accuracy, and reproducibility. The PGx platform is ideal for pre-clinical and discovery, as well as patient stratification and clinical trial support. Frontage is a CAP-accredited, CLIA-certified laboratory. 

Clinical validation shows accurate allele calls for multiple ADME genes.

Advantages of Frontage’s NGS PGx Platform:

  • Quick turn-around time 
  • High throughput workflow 
  • Genotyping >300 ADME-related genes 
  • Drug metabolism predictions for >100 pharmaceuticals 
  • Star allele calls based on numerous polymorphisms per gene 
  • Comprehensive, easy-to-understand report 
  • Validated for clinical use under CLIA/CAP