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- W2895870378 abstract "Equilibrium dialysis has been widely used for the measurement of the fraction of unbound drug (fu) in plasma, but it suffers from the accuracy and reliability for low fu values. To address this concern, an orthogonal approach, called the bidirectional equilibrium dialysis, is described to simultaneously measure a pair of fu values for each drug based on equilibration in 2 opposite dialysis directions: from plasma to buffer (fu,p/b) and from buffer to plasma (fu,b/p). Hypothetically, if true equilibrium is attained in both dialysis directions, the measured fu,b/p and fu,p/b values for a given drug should converge, and thus, the ratio of fu,b/p to fu,p/b becomes unity (1.0). Thus, the ratio can be used as a tangible readout for data reliability. This methodology has been extensively tested in the present study using various drugs with distinct plasma binding characteristics. Our results clearly showed that low fu values (<0.01) could be reliably determined and verified using either the standard or dilution bidirectional equilibrium dialysis method for some known highly bound drugs; for extensively bound drugs with high logD7.4, such as montelukast, bedaquiline, and venetoclax, only a range of fu can be reported with confidence because of uncertainty in the true equilibrium." @default.
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- W2895870378 date "2019-03-01" @default.
- W2895870378 modified "2023-10-10" @default.
- W2895870378 title "Improving Confidence in the Determination of Free Fraction for Highly Bound Drugs Using Bidirectional Equilibrium Dialysis" @default.
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- W2895870378 doi "https://doi.org/10.1016/j.xphs.2018.10.011" @default.
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