Wei Ziqin, Mu Hongfang, Zhang Xiaojing, Li Wenbin, Wang Rong
PLA Key Laboratory of the Plateau of the Environmental Damage Control, the 940th Hospital of Logistics Support Force of PLA, Lanzhou, 730050, China.
School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Curr Drug Deliv. 2024 Jun 27. doi: 10.2174/0115672018295087240620061102.
Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion. In recent years, increasing attention has been paid to the role of epigenetic modifications in regulating drug transporters under hypoxic conditions at high altitude. In this paper, we comprehensively review the effects of hypoxia on drug transporters and epigenetic modifications and explore the regulatory mechanism of epigenetic modifications on drug transporter expression under hypoxic conditions. The aim is to provide a reference for exploring the epigenetic regulation mechanism of drug transporter expression in the hypoxic environment at high altitude, and then guide the study of pharmacokinetics and promote effective and safe medication at high altitude.
药物转运体是影响缺氧条件下药物药代动力学的关键因素。研究表明，在缺氧环境中药物转运体水平会发生显著变化。除了受缺氧诱导因子-1、核受体和炎症因子调控外，缺氧还可通过表观遗传修饰来调节转运体，从而影响药物的吸收、分布、代谢和排泄。近年来，表观遗传修饰在高海拔缺氧条件下调节药物转运体中的作用受到越来越多的关注。本文全面综述了缺氧对药物转运体及表观遗传修饰的影响，并探讨了缺氧条件下表观遗传修饰对药物转运体表达的调控机制。目的是为探索高海拔缺氧环境中药物转运体表达的表观遗传调控机制提供参考，进而指导药代动力学研究并促进高海拔地区的有效安全用药。
