高原环境对药物药代动力学的影响：机制、临床意义与展望

Impact of a plateau environment on drug pharmacokinetics: mechanisms, clinical implications and perspectives

摘要

高原环境通过多机制交互作用系统调控药物药代动力学的吸收、分布、代谢和排泄全过程（ADME）。其中，低氧作为核心驱动因素，通过激活交感-肾上腺髓质轴、诱发血流动力学紊乱、损害胃肠屏障，以及调控药物代谢酶的活性和表达水平等多机制协同干扰ADME。不仅加剧了高原环境下药物作用的复杂性和不可预测性，也对临床用药安全构成严峻挑战。本文通过系统总结高原环境对药物ADME的动态调控机制以及人体病理生理改变与ADME的互作规律，为高原地区安全、高效、精准地使用药物提供理论依据和实践指导。

Abstract

The plateau environment dynamically regulates the entire pharmacokinetic process of drug absorption, distribution, metabolism, and excretion (ADME) through multi-mechanism interactions. Hypoxia, as the central driving factor, coordinately disrupts ADME by activating the sympathetic-adrenomedullary axis, inducing hemodynamic disturbances, impairing gastrointestinal barriers, and modulating the activity and expression levels of drug-metabolizing enzymes. These synergistic effects not only amplify the complexity and unpredictability of drug actions in a plateau environment but also pose critical challenges to clinical medication safety. This review systematically synthesized the regulatory mechanisms through which plateau conditions influence drug ADME and examined the interaction patterns between human pathophysiological adaptations and ADME alterations. It aimed at establishing a theoretical framework and practical guidance for ensuring safe, efficient, and precise drug administration in plateau regions.

关键词

高原 / 低氧 / 药代动力学 / 药物吸收 / 药物分布 / 肠道菌群

Key words

plateau / hypoxia / pharmacokinetics / drug absorption / drug distribution / intestinal flora

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基金资助

甘肃省科技重大专项计划资助项目(24ZDFA005)

甘肃省卫生行业优秀青年人才和骨干人才资助项目(GSWSQN2023-01)

甘肃省重点研发计划资助项目(23YFFA0034)

甘肃省联合科研基金重点项目(25JRRA1248)

兰州大学第一医院院内基金(ldyyyn2025-217)