title: In vitro suppression of drug-induced methaemoglobin formation by Intralipid(®) in whole human blood: observations relevant to the 'lipid sink theory'.
abstract: 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.
authors:  Research Registrar.
authors: T L
authors: TL
authors: Samuels
authors:  Associate Specialist.
authors: J W
authors: JW
authors: Willers
authors:  Consultant.
authors: D R
authors: DR
authors: Uncles
authors:  CT2 Trainee, Department of Anaesthesia, Worthing Hospital, Worthing, UK.
authors: R
authors: R
authors: Monteiro
authors:  CT2 Trainee, Department of Anaesthesia, Worthing Hospital, Worthing, UK.
authors: C
authors: C
authors: Halloran
authors:  Senior Lecturer in Statistics, Brighton University, Brighton, UK.
authors: H
authors: H
authors: Dai
mesh_terms: D000465:Algorithms; D001769:Blood / Q000187:drug effects*; D001784:Blood Gas Analysis; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008706:Methemoglobin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015233:Models, Statistical; D005996:Nitroglycerin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D012977:Sodium Nitrite / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005217:Fat Emulsions, Intravenous; D008055:Lipids; D014665:Vasodilator Agents; D008706:Methemoglobin; D005996:Nitroglycerin; D012977:Sodium Nitrite