Influence of CYP2B6*6 genotype on methadone metabolism. Shown is the plasma concentration versus time AUC ratio for EDDP/methadone for IV (A) R-methadone and (B) S-methadone and oral (C) R-methadone and (D) S-methadone, and the EDDP formation clearance for IV (E) R-methadone and (F) S-methadone and oral (G) R-methadone and (H) S-methadone. Results are shown as box plots (solid line within the box represents the median, dashed line within the box represents the mean, box boundaries are the 25th and 75th percentiles, error bars are the 10th and 90th percentiles, and individual points are outliers). *Significantly different from wild-type (CYP2B6*1/*1), P < 0.05. AUC = area under the curve; EDDP = 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine.