Premium
In vitro suppression of drug‐induced methaemoglobin formation by Intralipid ® in whole human blood: observations relevant to the ‘lipid sink theory’ *
Author(s) -
Samuels T. L.,
Willers J. W.,
Uncles D. R.,
Monteiro R.,
Halloran C.,
Dai H.
Publication year - 2012
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1111/j.1365-2044.2011.06914.x
Subject(s) - methemoglobin , medicine , sodium nitrite , in vitro , pharmacology , drug , chromatography , anesthesia , biochemistry , chemistry , hemoglobin , organic chemistry
Summary To provide further evidence for the lipid sink theory, we have developed an in vitro model to assess the effect of Intralipid ® 20% on methaemoglobin formation by drugs of varying lipid solubility. Progressively increasing Intralipid concentrations from 4 to 24 mg.ml −1 suppressed methaemoglobin formation by the lipid soluble drug glyceryl trinitrate in a dose‐dependent manner (p < 0.001). Both dose and timing of administration of Intralipid to blood previously incubated with glyceryl trinitrate for 10 and 40 min resulted in significant suppression of methaemoglobin formation (p < 0.0001 and p < 0.05, respectively). Mathematical modelling demonstrated that the entire process of methaemoglobin formation by glyceryl trinitrate was slowed down in the presence of Intralipid. Intralipid did not significantly suppress methaemoglobin formation induced by 2‐amino‐5‐hydroxytoluene (partially lipid soluble) or sodium nitrite (lipid insoluble; both p > 0.5). This work may assist determination of the suitability of drugs taken in overdose for which Intralipid might be deployed.