title: Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients.
abstract: OBJECTIVE
  Elevated serum proinflammatory cytokines are associated with the reduction of cytochrome P450 enzyme (CYP) activity. This study aimed to evaluate the oxycodone pharmacokinetics, central symptoms, and serum proinflammatory cytokines based on cachexia stage in cancer patients.
  
  
  METHODS
  Forty-seven cancer patients receiving extended-release oxycodone were enrolled. Predose plasma concentrations of oxycodone and its metabolites were normalized with the daily dose and body weight. The central symptoms and serum level of proinflammatory cytokines were investigated at each cachexia stage.
  
  
  RESULTS
  The plasma concentrations of oxycodone in patients with cachexia and refractory cachexia were significantly higher than that in patients with precachexia. The metabolic ratio to noroxycodone in patients with cachexia was significantly lower than that in patients with precachexia. The patients with a higher cachexia stage had a higher serum level of interleukin-6 (IL-6), but not tumor necrosis factor-α and interleukin-1β. The serum IL-6 level was correlated with the plasma concentration of oxycodone and inversely with the metabolic ratio to noroxycodone. The incidence of somnolence was not associated with the plasma oxycodone concentration. In contrast, the cachexia stage and its associated serum IL-6 level were correlated with the incidence of somnolence.
  
  
  CONCLUSIONS
  Cancer cachexia raised the plasma exposure of oxycodone through the reduction of CYP3A metabolic pathway. The reduction of CYP3A in cachectic cancer patients was associated with an elevation of serum IL-6. Although cachectic cancer patients with higher serum IL-6 levels had the symptom of somnolence, the alterations in oxycodone pharmacokinetics were not related to the incidence of symptom.
authors: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
authors: Hikaru
authors: H
authors: Sato
authors: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. naitou@hama-med.ac.jp.
authors: Takafumi
authors: http://orcid.org/0000-0002-7447-3789
authors: T
authors: Naito
authors: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
authors: Takuya
authors: T
authors: Ishida
authors: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
authors: Junichi
authors: J
authors: Kawakami
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002100:Cachexia / Q000097:blood* / Q000188:drug therapy; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D003693:Delirium / Q000139:chemically induced; D003863:Depression / Q000139:chemically induced; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D010098:Oxycodone / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D010098:Oxycodone; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A4; Cancer cachexia; Central symptom; Interleukin-6; Oxycodone; Pharmacokinetics