An in vitro assessment of the effect of intravenous lipid emulsion on total drug concentrations in human plasma utilising drugs commonly implicated in cardiovascular system poisoning.

Abstract

Background: The most commonly suggested mechanism of action for lipid emulsion (ILE) in poisoning is that it acts as an intravascular 'lipid-sink', allowing lipophilic drugs to bind with lipid molecules, reducing free plasma-drug concentrations. Little data exist assessing the interaction of ILE with drugs of varying lipid solubility. Objective(s): To assess the in vitro effect of ILE on total drug concentrations in human plasma exposed to various drugs implicated in cardiovascular system (CVS) poisoning and relate the findings to octanol:water coefficients of the drugs tested (LogP(octanol)). Method(s): Human plasma (1 mL samples) containing either amitriptyline, dothiepin, or clomipramine, verapamil or diltiazem, propranolol or atenolol, was incubated with 20% ILE (20, 100, 200 microlitres/mL) or equal volumes of phosphatebuffered saline (Control) in triplicate. Samples were centrifuged and the drug concentration in ILE-free plasma was assayed by GC/MS. Differences in drug concentrations between ILE and Control samples were expressed as percent-decrease ( +/- 95% CI) from Control. Unpaired t-test was used to compare drug concentrations between ILE samples and their respective Controls. Result(s): There were statistically significant decreases in ILE-treated plasma drug concentrations for the cyclic antidepressants and calcium channel-blockers. However, neither beta-blocker showed a significant decrease in drug concentrations at any ILE dose. Plasma drug concentrations fell more with increasing ILE concentration (See Table 1). Conclusion(s): A higher LogP(octanol) appears to correlate with in vitro reduction in plasma drug concentrations in the presence of ILE. Propranolol and atenolol, with the lowest LogP(octanol), did not exhibit significant sequestration into ILE. This technique may be a simple way to screen drugs for their potential binding to ILE. (Table Presented).