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Population Semiphysiologic Kinetic Modeling and Simulation of Plasma Triglyceride Levels After Soybean Oil–Based Intravenous Lipid Emulsion Administration in Rats
Author(s) -
Okada Akira,
Hirano Miyu,
Tanioka Maho,
Tsujimoto Takae,
Koyama Hikaru,
Nishimura Asako,
Shibata Nobuhito,
Fukushima Keizo,
Sugioka Nobuyuki
Publication year - 2017
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607116661030
Subject(s) - triglyceride , population , soybean oil , kinetics , apolipoprotein b , chemistry , bolus (digestion) , cholesterol , medicine , pharmacology , biochemistry , physics , environmental health , quantum mechanics
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.