Prevalence of Pharmacogenomic Evidence for the ADME Genes Related to Commonly Used Drugs
Authors: Deb Subrata , Cancel Andres , Reeves Anthony 
Published: June 2021

Background

Pharmacogenomics (PGx) is the study of genetic differences in multiple genes that influence the variability in drug response (efficacy and toxicity). The advantages of PGx application include optimization of patient therapy outcomes, improved drug alternatives and decreased healthcare costs. Genes related to absorption, distribution, metabolism and elimination (ADME) are susceptible to genetic polymorphisms and may influence the pharmacokinetic behavior of the medications. Clinical Pharmacogenetics Implementation Consortium (CPIC®) is a platform that advances the PGx practice by developing evidence‐based guidelines. The purpose of the present study was to analyze the involvement of ADME genes in the CPIC practice guidelines for the drugs for the fifteen most prevalent disease states in the United States.

Methods

The study analyzed for the drugs with ADME biomarkers genes (phase I drug metabolizing enzymes, phase II drug metabolizing enzymes and transporters) and level of evidence (A, B, C, D) in the CPIC database. CPIC evidence level A means a strong or moderate PGx intervention is recommended, whereas level B means a discretionary PGx action is recommended. For level C or level D no prescription changes are required due to either variable or very little PGx evidence available at this time. The fifteen most prevalent disease states in the United States were derived from the National Vital Statistics Reports of Centers for Disease Control and Prevention (CDC). The inclusion criteria consisted of drugs used in the treatment of most prevalent diseases as per the CDC reports and CPIC PGx evidence levels available on the CPIC website (www.cpicpgx.org). The exclusion criterion consisted of drugs that did not have CPIC level of evidence. The ADME gene‐related drugs were sorted out by CPIC level of evidence, number of prescriptions dispensed (ClinCalc database; www.Clincalc.com), and disease state. Data were organized and graphically analyzed using Microsoft Excel software.

Results

A total of 123 drugs related to ADME genes were identified from the CPIC database and levels of evidence were profiled. In general, a larger number of drugs are affected by the phase 1 enzyme PGx with a total of 49 drugs than the phase 2 enzyme or transporter PGx. Among the CPIC level of evidences, level D had the most drugs with a total of 55. CYP2D6 (n=25) had the most prevalence in CPIC level of evidence. The CPIC PGx evidence levels for genes‐related to phase I drug metabolizing enzymes were: level A 15 (31%), level B 17 (35%), level C 10 (20%) and level D 7 (14%). The evidence for phase II drug metabolizing enzymes were classified as: level A 3 (7%), level B 0 (0%), level C 6 (15%) and level D 32 (78%). The genes for transporters were found as: level A 1 (3%), level B 3 (9%), level C 13 (39%) and level D 16 (49%). The CPIC level A, C, and D had the most evidence for the drugs related to cancer, whereas CPIC level B had the most evidence for the drugs related depression.

Conclusion

The PGx intervention by the biomedical and clinical professionals through the knowledge of ADME‐gene related CPIC PGx guidelines for drugs will ensure patient safety, potentially minimize healthcare cost and facilitate new drug development in a targeted manner. Oncology and depression are the disease conditions with most drugs affected by ADME gene PGx.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.