Comparison of lipid sinks in sequestering common intoxicating drugs

Abstract

Intravenous lipid emulsion is a recommended treatment for local anesthetic intoxication. The lipid sink theory hypothesizes that the mechanism behind the lipid treatment is the entrapment of toxic drugs in plasma, preventing them from reaching target receptors. Lipid sink treatment has also been used as a last refuge treatment for severe tricyclic antidepressant intoxication with seemingly beneficial results. We selected three drugs, i.e. amiodarone, ketamine, and amitriptyline, that can cause severe intoxication and compared their interactions with two commercial fat emulsions (Intralipid® and ClinOleic®) and one synthetic liposome (80:20 mol% phosphatidylcholine/phosphatidylglycerol) dispersion. The interaction studies were carried out by capillary electrokinetic chromatography and the retention factors and distributions constants of the drugs were calculated. The results demonstrate that there is stronger interaction between the drugs and the synthetic liposome dispersion than with the commercial emulsions.

Resuscitation with Lipid Emulsion

“…With several mechanisms at work, our observations explain how ILE might provide benefit in the treatment of less-lipophilic drugs that also provoke cardiovascular toxicity such as baclofen 34 (LogD at pH 7.4 = −1.72) and lamotrigine 35–37 (LogD at pH 7.4 = −0.19). Extending this logic, the data also suggest that synthetic phospholipid dispersions designed to sequester drugs 38–40 may not reverse cardiotoxicity as effectively as ILE if they lack an inotropic effect. The mechanism that causes the inotropy is a matter of speculation, but additional mitochondrial processing of fatty-acids 16 increased energetic intermediates 41 , modulation of intrinsic signaling systems 42,43 or fatty-acid modification of Ca+ currents 16,44 could all play a role.…”

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

“…Undoubtedly, the future of detoxification is in toxin-specific emulsions and other suspensions including pH-gradient liposomes [20,21], other specially formulated liposomes [13,51–53] and macromolecular capture systems [54]. However, in the case of acute toxicity with cardiovascular collapse, capture in isolation may not optimize recovery.…”

“…However, without a clear understanding of their mechanism of action, some reservations remain as to their specific applicability [8–12]. The primary mechanism is often asserted to be an intravenous partitioning phenomenon, an effect which is supported by in vitro binding studies [13–15], isolated heart experiments [16], small animal experiments [17,18] and clinical reports [19]. This toxin–binding mechanism is both intuitive and relatively simple, and thus has stimulated efforts to optimize therapeutic formulations (e.g.…”

Capillary electromigration techniques for studying interactions between analytes and lipid dispersions

“…Our group has extensively studied the interaction of various drugs with artificial liposome dispersions and commercial lipid emulsions using a number of techniques, of which EKC has shown to be a fast and effective method for the calculation of drug distribution constants between the lipid and aqueous phases . In , the interaction between local anesthetics and extruded liposome dispersions of various compositions and commercial lipid emulsion was investigated.…”

“…Studies on the interaction of various drugs with Intralipid®, Clinoleic®, and artificial liposomes using a number of techniques were carried out in our group. The EKC methodology proved to be a fast and effective method for calculation of retention factor and the drug distribution constant between the lipid and aqueous phases . In order to determine the retention factors and distribution constants, the electrophoretic mobilities of lipid dispersions needed to be derived.…”