In vitro studies on intravenous fat emulsions used for detoxification: mechanisms of action and preclinical assessment tools

In vitro studies on intravenous fat emulsions used for detoxification: mechanisms of action and preclinical assessment tools

Poster

Delyan Krastev1, Vasil Atanasov2, Zahari Vinarov1, Slavka Tcholakova1, Nikolai Denkov1
1Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University
2Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University

The use of intravenous fat emulsions (IVFE) for treatment of drug intoxication still follows a trial-and-error approach, due to insufficient understanding of the mechanisms of the process and lack of predictive in vitro tools. We studied the physicochemical mechanisms of drug extraction from model plasma for seven drugs with clinical data for the detoxification efficiency of IVFE. Five of the studied drugs were labeled as “positive controls”, due to the reports of successful patient detoxification by IVFE, whereas the other two drugs did not respond to IVFE treatment. For all positive control drugs, drug extraction increased significantly with the increase of emulsion concentration, while the drug partition coefficient between model plasma and soybean oil (Keff) remained constant. Drug partitioning from the model plasma to the bulk of the emulsion oil droplets was identified as the primary scavenging mechanism, whereas adsorption on the oil-water interface did not play any role in the process. A threshold value of LogKeff = 1 could successfully discriminate between the positive controls (LogKeff > 1) and the non-respondents (LogKeff < 1). The described approach can be used to guide clinical practice in drug intoxication cases where a specific antidote is not available, expanding the treatment options of patients at intensive care conditions.
Keywords: Toxicology, intralipid, antidote, intoxication