背景:几种阿片类药物具有药物遗传和药物相互作用,这可能会损害其镇痛效果,但没有常规实施支持性疼痛管理。我们假设CYP2D6表型和同时使用CYP2D6底物或抑制剂与阿片类镇痛结果相关。
方法:在长期CYP2D6相关阿片类药物治疗(曲马多,氢吗啡酮,他喷他多或羟考酮)。代谢物表型(超尖[UM],正常[NM],中等[IM]或较差[PM])由CYP2D6基因型确定。社会人口统计学(性别,年龄,就业状况),临床(疼痛强度和缓解,神经性成分,生活质量,残疾,焦虑和抑郁),记录药理学(阿片类药物剂量和伴随药物治疗)和安全性(不良事件)变量.
结果:整个人口(66%为女性,65(14)岁,70%的人退休了,63%的人参加了下腰痛)被归类为PM(5%),IM(32%),NM(56%)和UM(6%)。多重线性和逻辑回归显示,当使用任何CYP2D6底物(p=0.022)或抑制剂(p=0.030)药物时,年轻时的疼痛强度和神经病变成分更高,分别,当存在CYP2D6抑制剂(p=0.030)时,疼痛缓解较差。
结论:在阿片类药物治疗CNCP期间伴随使用CYP2D6底物或抑制剂可能导致镇痛效果不足。这方面可能与CNCP管理期间的药理学决策有关。
BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes.
METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded.
RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present.
CONCLUSIONS: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.