Zhao Mengjing, Xing Huijie, Chen Min, Dong Dong, Wu Baojian
Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, Guangzhou, China.
Institution of Laboratory Animal, Jinan University, Guangzhou, China.
Xenobiotica. 2020 May;50(5):495-505. doi: 10.1080/00498254.2019.1672120. Epub 2019 Oct 1.
Metabolism and transport of many drugs oscillate with times of the day (solar time), resulting in circadian time-dependent drug exposure and pharmacokinetics.Time-dependent pharmacokinetics (also known as chronopharmacokinetics) is associated with time-varying drug effects and toxicity.This review summarizes drug-metabolizing enzymes and transporters with rhythmic expressions in the liver, intestine and/or kidney. Correlations of these diurnal proteins with circadian variations in drug exposure and effects/toxicity are covered. We also discuss the molecular mechanisms for circadian control of enzymes and transporters.Mechanism-based chronopharmacokinetics would facilitate a better understanding of chronopharmacology and the design of time-specific drug delivery systems, ultimately leading to improved drug efficacy and minimized toxicity.
许多药物的代谢和转运随一天中的时间（太阳时间）而波动，导致药物暴露和药代动力学呈现昼夜节律依赖性。时间依赖性药代动力学（也称为时辰药代动力学）与药物效应和毒性的时间变化有关。本综述总结了肝脏、肠道和/或肾脏中具有节律性表达的药物代谢酶和转运体。涵盖了这些昼夜蛋白与药物暴露及效应/毒性的昼夜变化之间的相关性。我们还讨论了酶和转运体昼夜控制的分子机制。基于机制的时辰药代动力学将有助于更好地理解时辰药理学以及设计时间特异性给药系统，最终提高药物疗效并将毒性降至最低。
