Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug‐drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure‐permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.

中文翻译：

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被动渗透性在设计成功药物中的关键作用。

被动渗透性是药物处置和递送的关键特性。它对于胃肠道吸收、大脑渗透、肾脏重吸收、确定清除机制和药物相互作用至关重要。被动扩散速率可在组织和动物物种之间转换，而吸收程度取决于药物特性以及体内生理学/病理生理学。已经开发出设计原则来指导药物化学以增强吸收，这结合了目标所要求的水溶性、渗透性和有时不利的化合物特性的平衡。已经实施了渗透性测定，能够快速发展结构-渗透性关系以改善吸收。减少非特异性结合和改善质量平衡的检测开发的未来进展将能够更准确地测量被动渗透性。整合效力、选择性、被动渗透性和其他 ADMET 特性的设计原则有助于将成功的候选药物快速推向患者。