title: Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Masaki
authors.initials: M
authors.lastname: Tashiro
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishida
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002100:Cachexia / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000097:blood; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D010098:Oxycodone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010111:Oxymorphone / Q000097:blood; D010146:Pain / Q000097:blood / Q000188:drug therapy
chemical_list: D000701:Analgesics, Opioid; D009019:Morphinans; C077256:noroxycodone; D010111:Oxymorphone; D010098:Oxycodone; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A
keywords: CYP2D6; cancer cachexia; oxycodone; oxymorphone; pharmacokinetics