Endogenous and iatrogenic sources of variability in response to opioid therapy in Post-Surgical and injured orthopedic patients

•The genetic factors predicting length of therapy were the genotypes of CYP2D6 and OPRM1.•The strongest factor predicting length of therapy was inhibitor adjusted CYP2D6 phenotype.•The modifiable factors predicting length of therapy are dose of hydrocodone and use of a CYP2D6 inhibitor. Hydrocodone is the most prescribed opioid in the US. The objective was to evaluate associations between genetic, intrinsic, and extrinsic patient factors, plasma hydrocodone and metabolites, common side effects, and pain scores in a cohort of orthopedic surgery patients. Data for each patient was collected by review of the electronic hospital record (EHR), and patient interview. Patients were recruited from those with trauma or undergoing scheduled elective surgery for total knee replacement or total hip at the University of Louisville Hospital, Baptist East Hospital, and Jewish Hospital, Louisville, KY. Plasma opiate concentrations and a targeted genotyping panel was performed. There were statistically significant correlations with daily (p