INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Exploring the ‘Lipid Sink’ as a mechanism for Reversal of Local Anesthetic Toxicity:A PBPK Modeling Study

Show full item record

Bookmark or cite this item:

Files in this item

File Description Format
PDF KUO_ILIN.pdf (2MB) (no description provided) PDF
Title: Exploring the ‘Lipid Sink’ as a mechanism for Reversal of Local Anesthetic Toxicity:A PBPK Modeling Study
Author(s): Kuo, Ilin
Advisor(s): Akpa, Belinda S.
Department / Program: Chemical Engineering
Graduate Major: Chemical Engineering
Degree Granting Institution: University of Illinois at Chicago
Degree: MS, Master of Science
Genre: Masters
Subject(s): Lipid rescue lipid emulsion lipid sink bupivacaine PBPK drug overdose intravenous lipid emulsion intralipid
Abstract: Intravenous lipid emulsions (ILE) have been demonstrated to be effective mitigators of systemic toxicity caused by drug overdose, with dramatic resuscitations observed in small animals and clinical settings. The prevailing theory as to their method of action is known as the ‘lipid sink’. The theory proposes that intravenous lipid droplets create a discrete hydrophobic phase in the blood stream into which lipophilic drugs preferentially partition. This partitioning is thought to reduce the quantity of drug that is accessible to tissues and thereby reduce the drug content of tissues in vital organs such as the heart. The objective of this work is to explore the validity of the proposed mechanism by quantitatively evaluating the impact of a sequestering droplet on the exposure of vital organs to acutely toxic concentrations of drug. This is achieved by: (i) development of a predictive physiologically based pharmacokinetic model for the study of the distribution, metabolism, and elimination of the local anesthetic bupivacaine; (ii) extension of the model to simulation of bupivacaine overdose and administration of intravenous lipid; (iii) assessment of the potential efficacy of a ‘lipid sink’ with regard to reducing tissue exposure to the anesthetic. The output of the model confirmed drug redistribution from tissues to the blood stream as an effect of the ‘lipid sink’ mechanism. It was observed that the efficacy of a lipid scavenger depends on a number of factors such as the lipid metabolism and the treatment regimen. Depending on the rate of lipid metabolism, ILE may cause a reduction in tissue exposure as low as 5% or as high as 35%. The model also predicts that ILE treatment is most effective when started early. The initial concentration drop in the heart tissue can be as high as 20% (5 minute treatment delay) or <10% (20 minute delay) Given the dramatic recoveries observed clinically, ILE therapy is clearly effective, but it is not clear that the sink mechanism is the primary mechanism of action (in the case of bupivacaine toxicity).
Issue Date: 2012-12-10
Genre: thesis
Rights Information: Copyright 2012 Ilin Kuo
Date Available in INDIGO: 2012-12-10
Date Deposited: 2012-05

This item appears in the following Collection(s)

Show full item record


Country Code Views
United States of America 529
China 71
United Kingdom 17
Russian Federation 17
India 16


My Account


Access Key