Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients
Relationships between oxycodone pharmacokinetics, central symptoms, and serum interleukin-6 in cachectic cancer patients
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DOI：
10.1007/s00228-016-2116-z
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发表时间：
2016-08
影响因子：
2.9
通讯作者：
Hikaru Sato;T. Naito;T. Ishida;J. Kawakami
中科院分区：
文献类型：
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作者：
Hikaru Sato;T. Naito;T. Ishida;J. Kawakami
目的血清促炎细胞因子水平升高与细胞色素P450酶（CYP 450）活性降低有关。本研究旨在评估羟考酮的药代动力学，中枢症状，恶病质阶段的癌症patients. MethodsForty 7癌症患者接受缓释羟考酮的基础上血清促炎细胞因子。羟考酮及其代谢产物的给药前血浆浓度随每日剂量和体重标准化。在每个恶病质stage.ResultsThe血浆羟考酮浓度在恶病质和难治性恶病质患者的中枢症状和血清中的促炎细胞因子的水平进行了调查，明显高于前恶病质患者。恶病质患者对去甲羟考酮的代谢率明显低于恶病质前期患者。恶病质分期越高，血清IL-6水平越高，而肿瘤坏死因子-α和IL-1β水平无明显差异。血清IL-6水平与羟考酮的血浆浓度相关，与去甲羟考酮的代谢率呈负相关。嗜睡的发生率与血浆羟考酮浓度无关。相反，恶病质阶段及其相关的血清IL-6水平与嗜睡的发病率。ConclusionsCancer恶病质通过减少CYP 3A代谢途径提高了羟考酮的血浆暴露。恶病质癌症患者CYP 3A的降低与血清IL-6的升高相关。尽管血清IL-6水平较高的恶病质癌症患者会出现嗜睡症状，但羟考酮药代动力学的改变与症状的发生无关。
PurposeElevated 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.MethodsForty-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.ResultsThe 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.ConclusionsCancer 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.