尿液中的阿片类生物标志物作为鸦片使用特征的可靠且有效的关联指标：一项为期10年的纵向评估。
Opioid biomarkers in urine as reliable and valid correlates of opium use characteristics: A 10-year longitudinal assessment.
作者信息
Naghash Mahdokht, Shaner Rebecca L, Poustchi Hossein, Roshandel Gholamreza, Williams Katrice D, Tuachi Abraham, Kamangar Farin, Boffetta Paolo, Abnet Christian C, Hamelin Elizabeth I, Freedman Neal D, Malekzadeh Reza, Etemadi Arash
机构信息
Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Emergency Response Branch, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.
出版信息
Drug Alcohol Depend Rep. 2025 Aug 30;17:100377. doi: 10.1016/j.dadr.2025.100377. eCollection 2025 Dec.
BACKGROUND
Biomarkers can clarify the mechanistic bases of health effects associated with opiate use and improve evaluating dose-response relationships by quantifying the absorbed dose through different routes and patterns of use, supporting the generalizability of opium research findings to broader opioid use.
METHODS
We recruited 449 individuals who used opium and 66 individuals who did not, 10 years after baseline evaluation in a cohort study. At both time points, we collected self-reported characteristics of opium use (route, frequency, type, and dose) and measured urinary concentrations of codeine, hydrocodone, hydromorphone, morphine, morphine-3-glucuronide, and morphine-6-glucuronide in spot urine samples. We used multivariate linear regression models to determine the independent effects of each opium use characteristic on biomarker concentrations. Reliability of biomarker concentrations over the 10-year interval was assessed using intraclass correlation coefficients (ICCs) from linear mixed-effect models.
RESULTS
At the follow-up, 229 (51.0 %) subjects used opium by ingestion, which showed a significant shift compared with baseline (24.4 % ingestion). In adjusted models, opium ingestion, daily use, and presence of opioid use disorder (OUD) were associated with higher concentrations of all opioid biomarkers compared with opium smoking, non-daily use, and absence of OUD, respectively. All opioid biomarkers showed significant dose-response relationships relative to self-reported doses. Biomarker concentrations peaked when opium was used 3-4 h before sample collection and declined afterwards, remaining detectable for several days. Biomarker measurements were reliable (ICCs between 0.69 and 0.78) over the 10-year interval.
CONCLUSIONS
Opioid biomarkers are valid markers of lifetime history, route, frequency, dose, and recency of opium use and OUD diagnosis, and demonstrate good long-term reliability.
背景
生物标志物可以阐明与阿片类药物使用相关的健康影响的机制基础，并通过量化不同使用途径和模式下的吸收剂量来改善剂量反应关系的评估，从而支持将鸦片研究结果推广到更广泛的阿片类药物使用情况。
方法
在一项队列研究的基线评估10年后，我们招募了449名使用鸦片的个体和66名未使用鸦片的个体。在两个时间点，我们收集了自我报告的鸦片使用特征（途径、频率、类型和剂量），并测量了即时尿样中可待因、氢可酮、氢吗啡酮、吗啡、吗啡-3-葡萄糖醛酸苷和吗啡-6-葡萄糖醛酸苷的尿浓度。我们使用多元线性回归模型来确定每种鸦片使用特征对生物标志物浓度的独立影响。使用线性混合效应模型的组内相关系数（ICC）评估生物标志物浓度在10年间隔内的可靠性。
结果
在随访时，229名（51.0%）受试者通过口服使用鸦片，与基线相比有显著变化（口服使用率为24.4%）。在调整模型中，与吸烟、非每日使用和无阿片类药物使用障碍（OUD）相比，口服鸦片、每日使用和存在OUD分别与所有阿片类生物标志物的较高浓度相关联。所有阿片类生物标志物相对于自我报告的剂量均显示出显著的剂量反应关系。当在样本采集前3-4小时使用鸦片时，生物标志物浓度达到峰值，随后下降，但在数天内仍可检测到。生物标志物测量在10年间隔内是可靠的（ICC在0.69至0.78之间）。
结论
阿片类生物标志物是鸦片使用的终生史、途径、频率、剂量和近期使用情况以及OUD诊断的有效标志物，并显示出良好的长期可靠性。
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