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The impact of low temperature on fraction unbound for plasma and tissue
Author(s) -
Ryu Sangwoo,
Novak Jonathan J.,
Patel Roshan,
Yates Phillip,
Di Li
Publication year - 2018
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2160
Subject(s) - chemistry , plasma protein binding , incubation , fraction (chemistry) , binding site , free fraction , plasma concentration , hypothermia , biophysics , biochemistry , chromatography , pharmacology , biology , medicine
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.