European journal of clinical pharmacology · 2012
Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients.
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Naito Takafumi, Tashiro Masaki, Yamamoto Keisuke, Ohnishi Kazunori, Kagawa Yoshiyuki, Kawakami Junichi
Аннотация
PURPOSE: Cancer cachexia is characterized by hypoalbuminemia and with the hepatic production of acute-phase proteins in response to malignant growth. The aim of this study was to evaluate the influence of cachexia on the pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients.
METHODS: Forty-seven Japanese patients receiving oxycodone extended-release tablets as a starting opioid for cancer pain were enrolled in this study. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone and noroxycodone were determined at the titration dose.
RESULTS: Seven patients had a GPS of 0, 21 a GPS of 1, and 19 had a GPS of 2. A higher GPS was significantly correlated with a higher oxycodone concentration and a lower concentration ratio of noroxycodone to oxycodone and significantly associated with a lower incidence of dose escalation and a higher incidence of central adverse reactions. Serum albumin, but not α(1)-acid glycoprotein and C-reactive protein, was inversely correlated with the free fraction of oxycodone. Serum albumin concentration was significantly associated with the incidence of dose escalation. In contrast, the free fraction of oxycodone and acute-phase proteins were not related to the clinical responses.
CONCLUSIONS: 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.
METHODS: Forty-seven Japanese patients receiving oxycodone extended-release tablets as a starting opioid for cancer pain were enrolled in this study. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone and noroxycodone were determined at the titration dose.
RESULTS: Seven patients had a GPS of 0, 21 a GPS of 1, and 19 had a GPS of 2. A higher GPS was significantly correlated with a higher oxycodone concentration and a lower concentration ratio of noroxycodone to oxycodone and significantly associated with a lower incidence of dose escalation and a higher incidence of central adverse reactions. Serum albumin, but not α(1)-acid glycoprotein and C-reactive protein, was inversely correlated with the free fraction of oxycodone. Serum albumin concentration was significantly associated with the incidence of dose escalation. In contrast, the free fraction of oxycodone and acute-phase proteins were not related to the clinical responses.
CONCLUSIONS: 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.