Population Semiphysiologic Kinetic Modeling and Simulation of Plasma Triglyceride Levels After Soybean Oil–Based Intravenous Lipid Emulsion Administration in Rats

Abstract

Background: Soybean oil–based intravenous lipid emulsion (SO-ILE) has clinical utility as an energy source and in lipid rescue therapy. However, an excessive infusion rate of SO-ILE in routine use and in lipid rescue therapy may cause serious side effects. There is little information about plasma triglyceride (TG) kinetics following SO-ILE administration. The present study aimed to develop a population semiphysiologic kinetic model of TG and to predict the TG kinetics even at extremely high concentrations in rats. Materials and Methods: TG concentration profiles after intravenous bolus (0.1, 0.25, 0.5, 1.0, 1.5, and 2.0 g/kg) or infusion (3.0 g/kg/h for 1 hour) of SO-ILE to rats were analyzed by a kinetic model constructed with 4 pathways: apolipoprotein acquisitions, zero-order catabolism, first-order uptake to storage sites, and zero-order secretion from storage sites. The developed model was subjected to internal and external validation. Results: Plasma TG concentrations appeared to decline in a biphasic manner with nonlinear TG kinetics. The developed kinetic model was well validated and found to accurately predict the external validation data. Conclusions: The proposed kinetic model accurately described TG concentrations after SO-ILE administration at various infusion rates, including a lipid rescue regimen. The maximum acceptable infusion rate of SO-ILE in routine use should correspond to the maximum velocity of the apolipoprotein acquisition: 0.619 g/kg/h in rats. The prediction of TG kinetics at extremely high concentrations will provide useful information for lipid rescue therapy.