Sánchez-Luquez Karen, Reis Silveira Anne Michelli, Sánchez-Vinces Salvador, Rosini Silva Alex Ap, Barreto Joyce, Lemos de Brito Rhubia Bethania Socorro, Garcia Caroline de Moura, Vieira Ana Lais, Antonio Marcia Ap, de Oliveira Carvalho Patrícia
Health Sciences Postgraduate Program, São Francisco University-USF, Bragança Paulista 12916-900, SP, Brazil.
Integrated Unit of Pharmacology and Gastroenterology (UNIFAG), São Francisco University-USF, Bragança Paulista 12916-900, SP, Brazil.
Pharmaceuticals (Basel). 2025 Jan 11;18(1):82. doi: 10.3390/ph18010082.
BACKGROUND/OBJECTIVES: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety.
Thirty-seven healthy volunteers, enrolled after rigorous health assessments, received a single dose of etodolac (Flancox 500 mg). Pharmacokinetic profiles were determined using tandem mass spectrometry analysis, and the metabolomic profiling was conducted using baseline samples (pre-dose) and samples at maximum drug concentration (post-dose) via liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Network analysis was employed to interpret the data.
Correlations were observed between metabolomic profiles and pharmacokinetic parameters as well as clinical characteristics. Notably, metabolites derived from arachidonic acid, such as prostaglandins and leukotrienes, were linked to etodolac's pharmacokinetics. Other metabolites involved in pathways like cholesterol biosynthesis, bile salts, riboflavin, and retinoic acid signaling were correlated with hematological and liver function parameters. These findings are consistent with the infrequent adverse events reported by participants, including hematological and biochemical changes in liver function.
A set of metabolites was identified in possible associations between specific pathways and unusual side effects, comparing the metabolic profiles before and after doses of etodolac. Our results highlight the importance of optimizing drug therapy and minimizing adverse events by taking into account individual metabolic profile information.
背景/目的：本研究调查了单剂量依托度酸在健康志愿者中的代谢谱，重点关注药代动力学、临床参数和代谢组学变化，以确定与药物反应、疗效和安全性相关的生物标志物和途径。
37名经过严格健康评估后入选的健康志愿者接受了单剂量依托度酸（氟痛克500毫克）。使用串联质谱分析法测定药代动力学谱，并通过液相色谱与四极杆飞行时间质谱仪联用，对基线样本（给药前）和最大药物浓度样本（给药后）进行代谢组学分析。采用网络分析来解释数据。
观察到代谢组学谱与药代动力学参数以及临床特征之间存在相关性。值得注意的是，源自花生四烯酸的代谢物，如前列腺素和白三烯，与依托度酸的药代动力学有关。参与胆固醇生物合成、胆汁盐、核黄素和视黄酸信号传导等途径的其他代谢物与血液学和肝功能参数相关。这些发现与参与者报告的罕见不良事件一致，包括肝功能的血液学和生化变化。
通过比较依托度酸给药前后的代谢谱，确定了一组代谢物与特定途径和异常副作用之间可能存在的关联。我们的结果强调了通过考虑个体代谢谱信息来优化药物治疗和最小化不良事件的重要性。
