Review of the pharmacological data on intravenous lipid emulsions

Introduction: Initially, the clinical application of lipid emulsions (LEs) was parenteral nutrition. Since 2006, LEs have been widely used as an antidote for various intoxications with lipophilic drugs. Despite the widespread use of LEs, there is insufficient information regarding their pharmacokinetics and mechanism of antidote action. That is why detailed knowledge of their pharmacokinetic parameters and complex mechanism of action is particularly important. Aim: The aim of the study is to make a detailed literature analysis of the pharmacokinetics and of all putative mechanisms of antidote action of LEs. Material s and Methods : Over 100 literature sources were studied in various databases, including PubMed, ScienceDirect, Research Gate, Google Scholar, and others. These include clinical cases (over 40), laboratory animal experiments (over 20), and medical guidelines and protocols (over 30). Results: Lipid emulsions have good absorption and 100% bioavailability after intravenous administration. They do not bind to plasma proteins. Lipid emulsions undergo hepatic metabolism similar to chylomicrons. Their plasma half-life is ±10 minutes. The osmolarity of LEs is 270-345 mosm/l. Lipid emulsions cross the blood-brain barrier but do not cross the placental barrier. They are mainly removed from skeletal muscles (47%), splanchnic organs (25%), myocardium (14%) and subcutaneous tissue (13%). LD 50 in rats is 67.72 mL/kg and in dogs 135 mL/kg. The maximum single harmless dose for a person (70 kg) is 4000–7000 mL/24 h. The most widely advocated mechanism of non-antidote action of LEs is the lipid uptake phenomenon. Conclusion: Evidence collected from numerous clinical cases and laboratory experiments shows high efficiency and great therapeutic safety. Lipid emulsions are distinguished by their ability to dissolve and absorb lipophilic xenobiotics. In the blood, LEs prevent their binding to target receptors or, through the concentration gradient, extract them from critical organs, such as the brain and heart. Lipid emulsions have a cardioprotective effect as energy donors for the myocardium. They also exhibit vasoconstriction, which is important for overcoming toxic shock. Therefore, LEs represent an important therapeutic tool in the fight against intoxications with lipophilic drugs, such as anesthetics, psychopharmacology, and cardiovascular drugs.