Cachexia had an effect on oxycodone metabolism and the clinical responses to oxycodone. The observed reduction in serum albumin concentration was associated with dose escalation. These findings suggest that cachexia affects the clinical responses to oxycodone through metabolic and nutritional disorders in cancer patients.

The aim of this study was to evaluate the plasma dispositions of oxycodone and its demethylates and dose escalation based on genetic polymorphisms of CYP2D6, CYP3A5, ABCB1, and OPRM1 in cancer patients receiving oxycodone. Sixty-two Japanese cancer patients receiving oxycodone extended-release tablets were enrolled. Predose plasma concentrations (C(12)) of oxycodone, noroxycodone, and oxymorphone were determined at the titrated dose. Daily oxycodone escalation rate was evaluated as the opioid escalation index (OEI). Genetic variants did not significantly alter oxycodone C(12). Oxymorphone C(12) and its ratio to oxycodone C(12) were significantly higher in CYP2D6 extensive metabolizers than in intermediate metabolizers but did not affect dose escalation. In contrast, noroxycodone C(12) and its ratio to oxycodone C(12) were significantly higher in the CYP3A5*1 carrier group than in the *3/*3 group. The OEI was significantly higher in the CYP3A5*3/*3 group than in the *1 carrier group. No significant difference was observed in the OEI in the other genetic variants. Noroxycodone C(12) was higher in the dose escalation group as compared to the nonescalation group and significantly affected the incidence of dose escalation. In conclusion, CYP3A5*3 altered the plasma disposition of noroxycodone, which was inversely affecting the dose escalation in cancer patients receiving oxycodone.

This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.