title: Population Semiphysiologic Kinetic Modeling and Simulation of Plasma Triglyceride Levels After Soybean Oil-Based Intravenous Lipid Emulsion Administration in Rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okada
authors.affiliation: 1 Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Hirano
authors.affiliation: 1 Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Tanioka
authors.affiliation: 2 Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Takae
authors.initials: T
authors.lastname: Tsujimoto
authors.affiliation: 3 Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Koyama
authors.affiliation: 4 Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyoto, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: 4 Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, Kyoto, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Shibata
authors.affiliation: 1 Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Fukushima
authors.affiliation: 1 Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugioka
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D008962:Models, Theoretical; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood*
chemical_list: D005217:Fat Emulsions, Intravenous; D014280:Triglycerides; D013024:Soybean Oil
keywords: lipid rescue therapy; modeling and simulation; parenteral nutrition; pharmacokinetic modeling; population study; soybean oil-based intravenous lipid emulsion; triglyceride