Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Genet Med. 2019 Aug;21(8):1842-1850. doi: 10.1038/s41436-018-0431-8. Epub 2019 Jan 23.
CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.
Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS measures.
On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n = 45) had greater improvement in the CYP2D6-guided versus usual care arm (-1.01 ± 1.59 vs. -0.40 ± 1.20; adj P = 0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (-0.61 ± 1.39) and usual care (-0.54 ± 1.69) groups (adj P = 0.540).
These data support the potential benefits of CYP2D6-guided pain management.
CYP2D6 可使可待因和曲马多生物转化，中效代谢者（IM）和低效代谢者（PM）的镇痛作用可能受损。这项实用的概念验证试验测试了 CYP2D6 指导的阿片类药物处方对疼痛控制的影响。
从 7 家诊所招募了患有慢性疼痛（94%使用阿片类药物）的参与者，采用聚类设计将其分为 CYP2D6 指导组（n=235）和常规护理组（n=135）。根据基因型和 CYP2D6 抑制剂的使用情况分配 CYP2D6 表型，在 CYP2D6 指导组中提出阿片类药物处方建议。使用 PROMIS 量表在基线和 3 个月时评估疼痛。
在逐步多元线性回归中，最初开处方曲马多/可待因的 IM/PM （n=45）的复合疼痛强度（当前疼痛和过去一周中最严重和平均疼痛的综合）主要结局在 CYP2D6 指导组优于常规护理组（-1.01±1.59 与 -0.40±1.20；调整后的 P=0.016）；CYP2D6 指导组中有 24%的参与者报告复合结局有≥30%（临床有意义）的改善，而常规护理组中则为 0%。相比之下，在基线时开处方曲马多或可待因的正常代谢者中，CYP2D6 指导组（-0.61±1.39）和常规护理组（-0.54±1.69）在 3 个月时复合疼痛强度的变化没有差异（调整后的 P=0.540）。
这些数据支持 CYP2D6 指导疼痛管理的潜在益处。
