Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients
Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients
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DOI：
10.1007/s00228-012-1266-x
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发表时间：
2012-10-01
影响因子：
2.9
通讯作者：
Kawakami, Junichi
中科院分区：
文献类型：
--
作者：
Naito, Takafumi;Tashiro, Masaki;Kawakami, Junichi
癌症恶病质的特征是低白蛋白血症和肝脏产生急性期蛋白以应对恶性生长。本研究的目的是评估癌症患者恶病质对羟考酮的药代动力学分布和临床反应的影响。本研究纳入了 47 名接受羟考酮缓释片作为起始阿片类药物治疗癌症疼痛的日本患者。使用格拉斯哥预后评分（GPS）评估恶病质。在滴定剂量下测定羟考酮和去甲羟考酮的给药前血浆浓度。7 名患者的 GPS 为 0，21 名患者的 GPS 为 1，19 名患者的 GPS 为 2。较高的 GPS 与较高的羟考酮浓度和较低的去甲羟考酮与羟考酮浓度比显着相关，并且与较低的剂量递增发生率和较高的中枢不良反应发生率显着相关。血清白蛋白，而不是α(1)-酸性糖蛋白和C-反应蛋白，与羟考酮的游离分数呈负相关。血清白蛋白浓度与剂量递增的发生率显着相关。相反，羟考酮和急性时相蛋白的游离部分与临床反应无关。恶病质对羟考酮代谢和对羟考酮的临床反应有影响。观察到的血清白蛋白浓度降低与剂量递增相关。这些发现表明，恶病质通过癌症患者的代谢和营养障碍影响对羟考酮的临床反应。
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.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.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 alpha(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.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.