Grahl Justin, Mills Megan, Singh Amit, Oxencis Carolyn, Mohr Alexander, Mancuso Taylor, Teng Bi Qing, Bajorunaite Ruta, Carver Thomas, Peppard William J
Froedtert & The Medical College of Wisconsin, Milwaukee, WI, USA.
ThedaCare Health Systems, Appleton, WI, USA.
Hosp Pharm. 2025 May 20:00185787251339360. doi: 10.1177/00185787251339360.
Opioids are utilized for acute pain in hospitalized patients and carry the risk of unintentional toxicity. The relationship between unintentional toxicity within a hospital setting and genetic polymorphisms has not been fully evaluated within the literature to date. Assessment and utilization of pharmacogenetic data may be a way to prevent unintentional toxicity in hospitalized patients and reduce the need for naloxone administration. This study aimed to provide proof of concept for the comparison of allele frequencies of hospitalized patients who received naloxone for opioid reversal with lab control data allele frequencies to identify variations between groups. This single-center, exploratory, pilot study enrolled 15 patients. Genotype samples were collected via buccal swab and analyzed using a custom 13 gene panel of genes which impact opioid metabolism. Genes assessed include . The 15 patients were compared to an internal lab control group of 100 patients and separated into preventable and not preventable events for further analysis. genotype was found to be statistically significantly different between the experimental and control groups ( = .004). This statistically significant difference was also seen in phenotypes ( = .038). When comparing preventable and not preventable events, a statistically significant difference was found in both the genotype ( = .030) and phenotype ( = .029) of . Other assessed risk factors included mean MME in the 24 hours preceding naloxone being higher among preventable events and hospital or emergency department admission percent risk being higher among not preventable events. Factors other than pharmacogenetics, including opioid route of administration, medication formulation, and overall hospital admission risk, may play an additive role in unintentional toxicity risk. Future research of genotype-guided opioid dosing in pain management services further adds to calculating the risk of unintentional opioid-related adverse effects with standard dosing of this drug class.
阿片类药物用于住院患者的急性疼痛治疗,但存在意外中毒风险。迄今为止,医院环境中的意外中毒与基因多态性之间的关系在文献中尚未得到充分评估。药物遗传学数据的评估和应用可能是预防住院患者意外中毒并减少纳洛酮使用需求的一种方法。本研究旨在通过比较接受纳洛酮进行阿片类药物逆转的住院患者的等位基因频率与实验室对照数据的等位基因频率,以提供概念验证,从而识别组间差异。这项单中心、探索性的试点研究招募了15名患者。通过口腔拭子收集基因型样本,并使用影响阿片类药物代谢的13个基因的定制基因面板进行分析。评估的基因包括……将这15名患者与100名患者的内部实验室对照组进行比较,并分为可预防和不可预防事件进行进一步分析。发现实验组和对照组之间基因型存在统计学显著差异(P = 0.004)。在表型上也观察到了这种统计学显著差异(P = 0.038)。在比较可预防和不可预防事件时,在……的基因型(P = 0.030)和表型(P = 0.029)中均发现了统计学显著差异。其他评估的风险因素包括:在可预防事件中,纳洛酮前24小时平均每日吗啡当量较高;在不可预防事件中,医院或急诊科入院风险百分比较高。除药物遗传学外的其他因素,包括阿片类药物给药途径、药物剂型和总体住院风险,可能在意外中毒风险中起累加作用。未来在疼痛管理服务中对基因型指导的阿片类药物剂量的研究进一步增加了计算使用此类药物标准剂量时意外阿片类药物相关不良反应风险的内容。