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全身性炎症：不可忽视的精准用药影响因素
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| 篇名： | 全身性炎症：不可忽视的精准用药影响因素 |
| TITLE： | Systemic inflammation：a nonnegligible factor in precision pharmacotherapy |
| 摘要： | 全身性炎症常见于感染、肿瘤、应激、衰老等病理生理状态，是影响药物代谢的重要非遗传因素。炎症状态下，白细胞介素-6（IL-6）、肿瘤坏死因子α等炎症指标经核因子κB等通路抑制细胞色素P450（CYP450）酶系及药物转运体表达，改变血浆蛋白结合与组织分布，使药物体内暴露偏离基因型预测，出现临床药物代谢表型与基因型不一致的表型转化，从而影响基于基因型、靶点表达及生理参数制定个体化用药决策的精准性。细胞因子中，IL-6对CYP3A4、CYP2C19、CYP2C9、CYP2D6等酶及P-糖蛋白等转运体影响广泛，IL-6抑制剂可逆转其对CYP450酶的抑制作用。将炎症基线及其动态轨迹作为时变协变量纳入群体药代动力学模型，并结合治疗药物监测与人工智能技术，有望实现炎症指标驱动的精准给药。本文综述全身性炎症对药物代谢酶和转运体的影响及分子机制，分析将炎症指标纳入个体化用药评估的挑战与前景，提出应重视全身性炎症这一系统性变量，加强基础与临床研究，将炎症状态及动态轨迹融入用药决策，有助于提升个体化用药的精准性。 |
| ABSTRACT： | ystemic inflammation， commonly observed in pathophysiological states such as infection， malignancy， stress， and aging， is an important non-genetic factor affecting drug metabolism. Under inflammatory conditions， inflammatory indicators such as interleukin-6 （IL-6） and tumor necrosis factor-α inhibit the expression of the cytochrome P450 （CYP450） enzyme system and drug transporters via pathways including nuclear factor-κB， and alter plasma protein binding and tissue distribution， causing in vivo drug exposure to deviate from genotype-based predictions and leading to phenoconversion， which is a discordance between the clinical drug-metabolizing phenotype and the drug-metabolizing genotype. This affects the precision of personalized medication decisions based on genotype， target expression， and physiological parameters. Among cytokines， IL-6 broadly affects enzymes such as CYP3A4， CYP2C19， CYP2C9， and CYP2D6 and transporters such as P-glycoprotein， while IL-6 inhibitors can reverse its inhibitory effects on CYP450 enzymes. Incorporating baseline inflammatory status and its dynamic trajectory as time-varying covariates into population pharmacokinetic models， in combination with therapeutic drug monitoring and artificial intelligence， is expected to enable inflammation-driven precision dosing. This article reviews the effects and molecular mechanisms of systemic inflammation on drug-metabolizing enzymes and transporters， analyzes the challenges and prospects of integrating inflammatory indicators into personalized pharmacotherapy assessment， and proposes that systemic inflammation， as a systemic variable， should be emphasized， with basic and clinical research strengthened and inflammatory status and its dynamic trajectory incorporated into medication decision-making， which may improve the precision of personalized pharmacotherapy. |
| 期刊： | 2026年第37卷第20期 |
| 作者： | 枉前 |
| AUTHORS： | WANG Qian |
| 关键字： | 全身性炎症;代谢表型;表型转化;白细胞介素-6;肿瘤坏死因子α;CYP450酶;转运体;精准用药 |
| KEYWORDS： | metabolic phenotype;phenoconversion;interleukin-6;tumor necrosis factor-α;CYP450 enzymes;transporter;precision pharmacotherapy |
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