在INGENIOUS试验中与曲马多和可待因治疗相关的药物-基因及药物-药物相互作用。
Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial.
作者信息
Fulton Cathy R, Zang Yong, Desta Zeruesenay, Rosenman Marc B, Holmes Ann M, Decker Brian S, Zhang Yifei, T Callaghan John, Pratt Victoria M, Levy Kenneth D, Gufford Brandon T, Dexter Paul R, Skaar Todd C, Eadon Michael T
机构信息
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Health Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN 46202, USA.
出版信息
Pharmacogenomics. 2019 Apr;20(6):397-408. doi: 10.2217/pgs-2018-0205. Epub 2019 Feb 20.
Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.
曲马多和可待因由CYP2D6代谢，且会发生药物-基因和药物-药物相互作用。这项中期分析研究了102名在接受药物基因分型（作为INGENIOUS试验[NCT02297126]的一部分）时开具曲马多或可待因处方的患者的用药行为和疗效。在接受曲马多或可待因治疗的60天内，与正常或代谢情况不确定的患者相比，临床医生更频繁地为超快代谢者和慢代谢者开具替代阿片类药物（比值比：19.0；95%置信区间：2.8-160.4）（p = 0.01）。在调整了药物-药物相互作用后的CYP2D6活性评分后，CYP2D6活性降低的患者中报告未得到控制的疼痛更为频繁（比值比：0.50；95%置信区间：0.25-0.94）。药物-药物和药物-基因相互作用的表型转化是药物基因组学实施中的一个重要考虑因素；药物-药物相互作用可能会掩盖基因分型的潜在益处。
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