Plasma Concentrations of Oral Oxycodone Are Greatly Increased in the Elderly

We compared the pharmacokinetics of 10 mg oral oxycodone in four groups of 10 patients each, aged 20–40, 60–70, 70–80, and 80–90 years. Patients aged 70–80 and 80–90 years had 50–80% higher mean exposure to oxycodone (P 70 years of age had more than twofold higher (P < 0.05) mean plasma oxycodone concentrations than the youngest age group. Regarding the metabolites of noroxycodone, oxymorphone, and noroxymorphone, the only statistically significant difference was in the mean t ½ of noroxycodone, which was 3 h longer in the 70–80 and 80–90 groups (P < 0.05) than in the 20–40 group (Table 2 and Figure 1). There were no significant gender-associated differences in any of the pharmacokinetic parameters. Effect of CYP2D6 genotype on oxycodone pharmacokinetics: Plasma oxycodone, noroxycodone, oxymorphone, and noroxymorphone concentrations in poor metabolizers, intermediate metabolizers, extensive metabolizers (EMs), and ultrarapid metabolizers (UMs) of CYP2D6 are shown in Figure 1. The corresponding metabolite-to-parent drug AUC ratios (AUC m / AUC p ) for oxymorphone, noroxycodone, and noroxymorphone are shown in Figure 2. The poor metabolizer and intermediate metabolizer patients appeared to have higher plasma oxycodone and noroxycodone concentrations and lower oxymorphone and noroxymorphone concentrations than the EM and UM patients did, irrespective of age. Effect of concomitantly used drugs on oxycodone pharmacoki netics: The patient taking carbamazepine had distinctly different pharmacokinetic parameters as compared to other patients. For example, her oxycodone AUC 0–∞ was 19% and oxycodone t ½ was 46% of the corresponding mean values of other patients in her age group. She also had the shortest noroxycodone t ½ .