A physiologically based in silico kinetic model predicting plasma cholesterol concentrations in humans.

摘要: Increased plasma cholesterol concentration is associated with increased risk of cardiovascular disease. This study describes the development, validation, and analysis a physiologically based kinetic (PBK) model for prediction concentrations in humans. was directly adapted from PBK mice by incorporation reaction catalyzed ester transfer protein contained 21 biochemical reactions eight different pools. The calibrated using published data humans validated comparing predictions on levels subjects 10 genetic mutations (including familial hypercholesterolemia Smith-Lemli-Opitz syndrome) experimental data. Average total were accurate within 36% data, which margin. Sensitivity indicated that HDL (HDL-C) mainly dependent hepatic transport to HDL, non-HDL, uptake non-HDL-C. Thus, presented valid tool predict effect concentrations, opening way future studies drugs various subpopulations silico. Copyright © 2012 American Society Biochemistry Molecular Biology, Inc.