Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study
Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study
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DOI：
10.1007/s00228-011-1093-5
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Dale, Ola
中科院分区：
文献类型：
--
作者：
Andreassen, Trine Naalsund;Eftedal, Ingrid;Dale, Ola
目的世界卫生组织推荐阿片类药物治疗中度至重度癌症疼痛。羟考酮是最常用的阿片类药物之一，在肝脏中通过CYP 3A 4和CYP 2D 6酶代谢。本横断面研究的目的是评估之间的关系羟考酮的药代动力学，药效学和CYP 2D 6基因型“弱代谢者”（PM），“快代谢者”（EM）和“超快速代谢者”（URM）在一个队列的癌症pain.Methods患者的基因型为最常见的CYP 2D 6变异体和羟考酮和代谢产物的血清浓度进行了测定。使用简明疼痛量表（BPI）评估疼痛。使用EORTC QLQ-C30评估疲乏和恶心症状。认知功能通过简易精神状态（MMS）检查进行评估。结果27例PM、413例EM（包括杂合子）和10例URM，其中10例为正常人，10例为非正常人。PM的羟吗啡酮和去甲羟吗啡酮血清浓度以及羟吗啡酮与羟考酮的比值低于EM和URM。结论CYP 2D 6基因型在药代动力学上存在预期差异，但对药效学无影响。CYP 2D 6基因型不影响疼痛控制，不良症状恶心和镇静或认知功能障碍的风险，在这项研究中，患者接受羟考酮治疗癌症疼痛。
Objective Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser" (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a cohort of patients with cancer pain.Methods The patients were genotyped for the most common CYP2D6 variants and serum concentrations of oxycodone and metabolites were determined. Pain was assessed using the Brief Pain Inventory (BPI). The EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive function was assessed by the Mini Mental State (MMS) examination. Associations were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal logistic regressions with and without covariates.Results The sample consisted of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than EM and URM. No differences between PM, EM and URM in pain intensity, nausea, tiredness or cognitive function was found.Conclusion CYP2D6 genotypes caused expected differences in pharmacokinetics, but they had no pharmacodynamic consequence. CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in this study of patients treated with oxycodone for cancer pain.