Department of Analytical Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151, Lodz, Poland.
Mol Biol Rep. 2020 Apr;47(4):3221-3231. doi: 10.1007/s11033-020-05361-2. Epub 2020 Mar 5.
Drug-protein binding plays a key role in determining the pharmacokinetics of a drug. The distribution and protein binding ability of a drug changes over a lifetime, and are important considerations during pregnancy and lactation. Although proteins are a significant fraction in plasma composition, they also exist beyond the bloodstream and bind with drugs in the skin, tissues or organs. Protein binding influences the bioavailability and distribution of active compounds, and is a limiting factor in the passage of drugs across biological membranes and barriers: drugs are often unable to cross membranes mainly due to the high molecular mass of the drug-protein complex, thus resulting in the accumulation of the active compounds and a significant reduction of their pharmacological activity. This review describes the consequences of drug-protein binding on drug transport across physiological barriers, whose role is to allow the passage of essential substances-such as nutrients or oxygen, but not of xenobiotics. The placental barrier regulates passage of xenobiotics into a fetus and protects the unborn organism. The blood-brain barrier is the most important barrier in the entire organism and the skin separates the human body from the environment.
药物-蛋白结合在决定药物的药代动力学方面起着关键作用。药物的分布和蛋白结合能力会随时间发生变化，在妊娠和哺乳期是需要重点考虑的因素。尽管蛋白质是血浆成分中的重要组成部分，但它们也存在于血液之外，并与皮肤、组织或器官中的药物结合。蛋白结合会影响活性化合物的生物利用度和分布，并且是药物跨生物膜和屏障转运的限制因素：药物通常无法穿过细胞膜，主要是由于药物-蛋白复合物的分子量很高，导致活性化合物的积累，并显著降低其药理活性。本文综述了药物-蛋白结合对药物穿过生理屏障转运的影响，这些屏障的作用是允许必需物质（如营养物质或氧气）通过，但不能让外源性物质通过。胎盘屏障调节外源性物质进入胎儿的过程，保护未出生的生物体。血脑屏障是整个机体最重要的屏障，皮肤将人体与环境分隔开。
