Pharmacogenomic Determinants of Concomitant Opioid Use in Chronic Low Back Pain Patients: A Preliminary Review

Purpose: The aim of this study is to provide pharmacogenetic information on opioid user profiles to better understand the inter-individual variability in drug response and provide guidance to healthcare providers. One of the major mechanisms of opioid metabolism is through hepatic cytochrome P-450 CYP2D6 enzymatic activity which predominately converts codeine to morphine and then morphine-6-glucuronide leading to therapeutic analgesic effects. The association of the CYP2D6 metabolizer phenotypes with formation of morphine via this pathway is well known. Codeine serves as a Prototype for Opioid Metabolism and Analgesia. The “extensive metabolizer” phenotype represents patients who experience normal analgesia at recommended opioid doses. However, the three other CYP2D6 metabolizer phenotypes present clinical challenges in opioid prescribing. At one end of the spectrum, “ultra-rapid metabolizers” are at high risk of opioid toxicity due to increased conversion of codeine to morphine. Alternatively, “poor metabolizers” lack opioid response because of decreased conversion to morphine. However, such patients may paradoxically experience opioid side effects if the dose is increased in efforts to achieve analgesia. Finally, “intermediate metabolizers” may not achieve adequate analgesia at recommended opioid doses and must be closely monitored to balance potential benefits and risks of therapy. Pharmacokinetic and pharmacodynamic studies of opioids such as tramadol and oxycodone similarly show that these drugs depend on CYP2D6 for conversion to active metabolites responsible for analgesia. Methods: DNA Genotyping using Scanner (Illumina) and precision medicine array. CYP2D6, CYP2C9 and CYP2C19 SNP panels, and the genotypes for all SNPs within these three genes are specifically mined from the microarray data for the purposes of risk characterization and cohort grouping. Results/Conclusions: Patients enrolled in the PRECISION TEXAS Pain Registry provide updated data to the baseline information. Selected baseline characteristics of the 40 registry patients enrolled during the first three months of low-intensity operation are available, including scores for pain intensity (11-point numerical rating scale), back-specific functioning (Roland-Morris Disability Questionnaire), quality of life (Patient-Reported Outcomes Measurement Information System-29 [PROMIS- 29]), pain catastrophizing, and pain self-efficacy.