Dhieb Dhoha, Anwardeen Najeha, Velayutham Dinesh, Elrayess Mohamed A, Jithesh Puthen Veettil, Bastaki Kholoud
Pharmaceutical Sciences Department, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
Pharmaceuticals (Basel). 2025 Jun 27;18(7):971. doi: 10.3390/ph18070971.
: Tramadol is an opioid frequently prescribed for moderate to severe pain and has seen a global increase in use. This presents numerous challenges in clinical management. This study aims to elucidate metabolic signatures associated with tramadol consumption, enhancing predictive capabilities for therapeutic outcomes and optimizing patient-specific treatment plans. : Data were obtained from the Qatar Biobank (QBB), focusing on pharmacogenomic variants associated with tramadol use and prescription trends. A cohort of 27 individuals who were administered daily tramadol doses between 100 and 400 mg with available metabolomic profiles were selected. The pharmacokinetics of tramadol were evaluated in relation to specific CYP2D6 genetic variants. Comparative pharmacometabolomic profiles were generated for tramadol users versus a control group of 54 non-users. Additionally, prescription data encompassing tramadol formulations were collected from the electronic medical records (EMR) system of the major public hospital network in Qatar (Hamad Medical Corporation) to discern prescribing patterns. : From January 2019 to December 2022, tramadol prescriptions varied, with chronic pain as the primary indication, followed by acute pain. Pharmacogenomic analysis indicated that CYP2D6 allele variations significantly impacted tramadol and O-desmethyltramadol glucuronide levels, notably in 'normal metabolizers'. Metabolomic analysis revealed distinct metabolic profiles in tramadol users, with significant variations in phosphatidylcholine, histidine, and lysine pathways compared to controls, highlighting tramadol's unique biochemical impacts. : This study underscores the importance of integrating genetic and omics-based approaches to enhance tramadol's efficacy and safety. These findings support personalized pain management strategies, enhancing treatment outcomes for both chronic and acute pain.
曲马多是一种常用于治疗中度至重度疼痛的阿片类药物，其全球使用量呈上升趋势。这给临床管理带来了诸多挑战。本研究旨在阐明与曲马多使用相关的代谢特征，提高对治疗效果的预测能力，并优化针对个体患者的治疗方案。
数据来自卡塔尔生物银行（QBB），重点关注与曲马多使用和处方趋势相关的药物基因组变异。选取了27名每天服用100至400毫克曲马多且有可用代谢组学数据的个体。评估了曲马多的药代动力学与特定CYP2D6基因变异的关系。生成了曲马多使用者与54名非使用者对照组的比较药物代谢组学图谱。此外，还从卡塔尔主要公立医院网络（哈马德医疗公司）的电子病历（EMR）系统收集了包含曲马多制剂的处方数据，以识别处方模式。
2019年1月至2022年12月期间，曲马多处方情况各异，主要适应症为慢性疼痛，其次是急性疼痛。药物基因组分析表明，CYP2D6等位基因变异显著影响曲马多和O - 去甲基曲马多葡萄糖醛酸水平，尤其是在“正常代谢者”中。代谢组学分析揭示了曲马多使用者独特的代谢图谱，与对照组相比，磷脂酰胆碱、组氨酸和赖氨酸途径存在显著差异，突出了曲马多独特的生化影响。
本研究强调了整合基于基因和组学的方法以提高曲马多疗效和安全性的重要性。这些发现支持个性化疼痛管理策略，改善慢性和急性疼痛的治疗效果。
