Bile acid kinetic modeling in end-stage liver support patients

Background & Aims: Solute generation rates, distribution volumes and compartment effects control the in vivo efficiency of any extracorporeal therapy such as extracorporeal liver support (ELS) used to remove bile acids accumulating in acute-on-chronic liver patients. The aim of this study was to identify and to examine kinetic parameters of two major bile acids using mathematical modeling. Methods: The kinetics of cholic (CA) and chenodeoxycholic acid (CDCA) were described by one- and two-compartment models with central elimination by decreasing or constant extracorporeal clearance, constant bile acid generation rate, and constant apparent distribution volume. Concentration profiles collected in 13 ELS sessions done in 8 patients were included for model calculations Results: For the one-compartment model, the average volumes and generation rates were 30 +/- 6 [l], 0.19 +/- 0.06 [mu mol/min] for CA and 22 +/- 5 [l], 0.29 +/- 0.08 [mu mol/min] for CDCA, respectively. For the one-compartment model and average normalized concentrations, the volumes and generation rates were 25 [l], 0.28 [mu mol/min] for CA and 18 [l], 0.37 [mu mol/min] for CDCA, respectively. For the two-compartment model, average normalized concentrations, the same initial concentration in both compartments, and assuming a 10% post-treatment rebound, the volume and generation rates were 25 [l], 0.27 [mu mol/min] for CA and 19 [l], 0.32 [mu mol/min] for CDCA, respectively. Conclusions: The generation rate for CDCA is higher when compared to that of CA and independent of the number of compartments. Assuming a constant extracorporeal clearance overestimates generation rate and distribution volume. The kinetic parameters of oneand two-compartment models are comparable for the same bile acid. (c) 2020 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.