Ryu Sangwoo, Novak Jonathan J, Patel Roshan, Yates Phillip, Di Li
Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Groton, CT, 06340, USA.
Early Clinical Development, Pfizer Inc., Cambridge, MA, 02139, USA.
Biopharm Drug Dispos. 2018 Nov;39(9):437-442. doi: 10.1002/bdd.2160. Epub 2018 Nov 13.
The effect of low temperature (4 °C) on plasma protein binding and tissue binding was evaluated for the first time using a large set of structurally diverse compounds covering a wide range of physiochemical properties and fraction unbound values. These results show that temperature has little effect on plasma protein binding and tissue binding and that the measured binding values at 4 °C are equivalent, on average, to those at physiological temperature (37 °C). The exception is indomethacin, where binding component(s) changed during long incubation at 37 °C. These data suggest that binding experiments can be conducted at 4 °C for unstable compounds in early drug discovery. Furthermore, plasma protein binding and tissue binding are likely to have little change during hypothermia conditions.
首次使用大量结构多样、涵盖广泛物理化学性质和未结合分数值的化合物，评估了低温（4°C）对血浆蛋白结合和组织结合的影响。这些结果表明，温度对血浆蛋白结合和组织结合影响很小，并且在4°C下测得的结合值平均与生理温度（37°C）下的相当。吲哚美辛是个例外，其结合成分在37°C长时间孵育期间发生了变化。这些数据表明，在药物早期发现中，对于不稳定化合物，可在4°C下进行结合实验。此外，在体温过低的情况下，血浆蛋白结合和组织结合可能变化很小。
