In silico modeling of nonspecific binding to human liver microsomes.

Estimation of unbound fraction of substrate in microsomal incubation media is important in accurately predicting hepatic intrinsic clearance and drug-drug interactions. In this study, the unbound fraction of 1223 drug-like molecules in human liver microsomal incubation media has been determined using equilibrium dialysis. These compounds, which include 27 marketed drug molecules, cover a much broader range of physiochemical properties such as hydrophobicity, molecular weight, ionization state, and degree of binding than those examined in previous work.