PI-44Correlation of CYP2D6 genotype with response to oxycodone in orthopedic injury related pain

Abstract

BACKGROUND Inter-individual variability in response and adverse effects to oxycodone in pediatric patients may be due to CYP2D6 enzyme genetic variation. Intermediate or poor metabolizer (IM, PM) genotypes have impaired oxymorphone formation and may have altered response to oxycodone. This study assessed clinical response and presence of adverse events of oxycodone treatment as a function of CYP2D6 genotype. METHODS Randomized double blind prospective clinical trial in a tertiary care emergency department. 66 children (6–18 y) with orthopedic injuries were randomized to single dose oxycodone (0.1, 0.15 or 0.2 mg/kg). DNA was obtained via buccal swab and CYP2D6 genotype determined. Pain was assessed by Faces Pain Scale (FPS) at baseline, and 20, 40 and 60 minutes post-dose. RESULTS Dose groups were comparable for demographics and baseline FPS scores. Each group had effective analgesia as evidenced by significant reduction of FPS scores from baseline (p < 0.001). No FPS score differences were demonstrated between dose groups at any time point. No significant adverse events occurred. One patient was a PM (mean FPS = 5.5). IM (n=15, FPS = 3.4 ± 2.6) reported lower FPS scores than extensive metabolizers (EM) reported (n=36, FPS = 4.7 ± 3.0). A GEE model accounted for repeated measures, and found the difference between EM and IM was non-significant (model coefficient 0.88 (-0.20, 1.97), p = 0.11). CONCLUSION Findings suggest clinical response to oxycodone varies with CYP2D6 genotype but further study is indicated. Clinical Pharmacology & Therapeutics (2005) 79, P18–P18; doi: 10.1016/j.clpt.2005.12.065