药效学
药品
药代动力学
药理学
停留时间(流体动力学)
药物发现
化学
计算生物学
医学
生物
生物化学
工程类
岩土工程
作者
Kevin E. Knockenhauer,Robert A. Copeland
摘要
A dominant assumption in pharmacology throughout the 20th century has been that in vivo target occupancy—and attendant pharmacodynamics—depends on the systemic concentration of drug relative to the equilibrium dissociation constant for the drug–target complex. In turn, the duration of pharmacodynamics is temporally linked to the systemic pharmacokinetics of the drug. Yet, there are many examples of drugs for which pharmacodynamic effect endures long after the systemic concentration of a drug has waned to (equilibrium) insignificant levels. To reconcile such data, the drug–target residence time model was formulated, positing that it is the lifetime (or residence time) of the binary drug–target complex, and not its equilibrium affinity per se, that determines the extent and duration of drug pharmacodynamics. Here, we review this model, its evolution over time, and its applications to natural ligand‐macromolecule biology and synthetic drug–target pharmacology.
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