---
title: "In vitro assessment of drug detoxification by intravenous fat emulsions and mechanism of action"
id: "pubmed-42572993"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42572993"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42572993/"
doi: "10.1080/15563650.2026.2708998"
published_at: "2026-08-10T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# In vitro assessment of drug detoxification by intravenous fat emulsions and mechanism of action
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42572993
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42572993/)
- **DOI:** [10.1080/15563650.2026.2708998](https://doi.org/10.1080%2F15563650.2026.2708998)
- **Published At:** 2026-08-10T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study evaluated physicochemical mechanisms by which **intravenous fat emulsions** extract drugs from model plasma using in vitro experiments. - Seven drugs were tested: bromazepam, bupivacaine, diphenhydramine, mepivacaine, quetiapine, paracetamol and verapamil. - Based on prior clinical reports, five of the drugs were classified as **responders** to lipid emulsion treatment and two as **non-responders**; the source abstract does not list which drugs were assigned to each group. - Drug extraction from model plasma rose significantly with increasing emulsion concentration for all responder drugs in the study. - The measured drug partition coefficient between model plasma and the intravenous fat emulsion (Intralipid®) was around or above **10** for responder drugs, meaning drug concentration in the lipid phase was roughly tenfold higher than in model plasma. - The primary scavenging mechanism identified was **partitioning** of drug into the bulk oil droplets of the emulsion; adsorption at the oil–water interface was not a contributing factor in these experiments. - A threshold partition coefficient of 10 was proposed to discriminate drugs likely to partition into intravenous lipid emulsions and therefore have potential clinical detoxification efficiency. - The authors suggest the described in vitro approach and threshold could guide clinical decision-making in intoxications when no specific antidote exists, potentially expanding treatment options in intensive care. - The article emphasizes that current clinical use of lipid emulsions for drug intoxication has been empirical and that better mechanistic understanding and predictive in vitro tools are needed. - Keywords highlighted by the source include: Intravenous fat emulsion; drug toxicity; in vitro; partitioning; scavenging mechanism.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # _In vitro_ studies of detoxification by intravenous fat emulsions: mechanism of action and preclinical assessment tools [Delyan Krastev](https://pubmed.ncbi.nlm.nih.gov/?term=Krastev+D&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria."), [Vasil Atanasov](https://pubmed.ncbi.nlm.nih.gov/?term=Atanasov+V&cauthor_id=42572993)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-2 "Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-3 "Department of Toxicology, Military Medical Academy, Sofia, Bulgaria."), [Zahari Vinarov](https://pubmed.ncbi.nlm.nih.gov/?term=Vinarov+Z&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-4 "BIORESOURCES BG, Plovdiv, Bulgaria."), [Slavka Tcholakova](https://pubmed.ncbi.nlm.nih.gov/?term=Tcholakova+S&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria."), [Nikolai Denkov](https://pubmed.ncbi.nlm.nih.gov/?term=Denkov+N&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#full-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.") Affiliations Expand ### Affiliations * 1 Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria. * 2 Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria. * 3 Department of Toxicology, Military Medical Academy, Sofia, Bulgaria. * 4 BIORESOURCES BG, Plovdiv, Bulgaria. * PMID: **42572993** * DOI: [ 10.1080/15563650.2026.2708998 ](https://doi.org/10.1080/15563650.2026.2708998) Item in Clipboard # _In vitro_ studies of detoxification by intravenous fat emulsions: mechanism of action and preclinical assessment tools Delyan Krastev et al. Clin Toxicol (Phila). 2026. Show details Display options Display options Format Abstract PubMed PMID Clin Toxicol (Phila) Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Clin+Toxicol+%28Phila%29%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Clin+Toxicol+%28Phila%29%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42572993/) . 2026 Aug 10:1-12. doi: 10.1080/15563650.2026.2708998. Online ahead of print. ### Authors [Delyan Krastev](https://pubmed.ncbi.nlm.nih.gov/?term=Krastev+D&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria."), [Vasil Atanasov](https://pubmed.ncbi.nlm.nih.gov/?term=Atanasov+V&cauthor_id=42572993)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-2 "Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-3 "Department of Toxicology, Military Medical Academy, Sofia, Bulgaria."), [Zahari Vinarov](https://pubmed.ncbi.nlm.nih.gov/?term=Vinarov+Z&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-4 "BIORESOURCES BG, Plovdiv, Bulgaria."), [Slavka Tcholakova](https://pubmed.ncbi.nlm.nih.gov/?term=Tcholakova+S&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria."), [Nikolai Denkov](https://pubmed.ncbi.nlm.nih.gov/?term=Denkov+N&cauthor_id=42572993)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42572993/#short-view-affiliation-1 "Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria.") ### Affiliations * 1 Department of Chemical and Pharmaceutical Engineering, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria. * 2 Department of Analytical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, Sofia, Bulgaria. * 3 Department of Toxicology, Military Medical Academy, Sofia, Bulgaria. * 4 BIORESOURCES BG, Plovdiv, Bulgaria. * PMID: **42572993** * DOI: [ 10.1080/15563650.2026.2708998 ](https://doi.org/10.1080/15563650.2026.2708998) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Introduction:** The use of intravenous fat emulsions for treatment of drug intoxication still follows a trial-and-error approach, due to insufficient understanding of the mechanisms of the process and lack of predictive _in vitro_ tools. **Methods:** We studied the physicochemical mechanisms of drug extraction from model plasma for seven drugs (bromazepam, bupivacaine, diphenhydramine, mepivacaine, quetiapine, paracetamol and verapamil) with clinical data for the detoxification efficiency of intravenous fat emulsions. Five of the studied drugs were labeled as "responders," due to clinical reports of successful patient detoxification, whereas the other two drugs were "non-responders," as they did not respond to intravenous fat emulsion treatment. **Results:** For all responders, drug extraction increased significantly with the increase of emulsion concentration, while the drug partition coefficient between model plasma and intravenous fat emulsion (Intralipid®) remained around or above 10: _viz_. the concentration of drug in the lipid phase was ten‑fold higher than in its concentration in the model plasma. **Discussion:** Drug partitioning from the model plasma to the bulk of the emulsion oil droplets was identified as the primary scavenging mechanism, whereas adsorption on the oil-water interface did not influence the process. For the studied seven drugs, it was established that a threshold value of 10 of the drug partition coefficient between model plasma and intravenous lipid emulsion can be successfully used to discriminate between drugs for which intravenous fat emulsions can lead to partitioning, indicating potential clinical efficiency in detoxification. **Conclusion:** The approach described can be used to guide clinical practice in drug intoxication cases where a specific antidote is not available, expanding the treatment options of patients in intensive care conditions. **Keywords:** Intravenous fat emulsion; drug toxicity; in vitro; partitioning; scavenging mechanism. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas. ](https://pubmed.ncbi.nlm.nih.gov/36321557/) Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P.Crider K, et al.Cochrane Database Syst Rev. 2022 Feb 1;2(2022):CD014217. doi: 10.1002/14651858.CD014217.Cochrane Database Syst Rev. 2022.Update in: [Cochrane Database Syst Rev. 2026 Feb 18;2:CD014217. doi: 10.1002/14651858.CD014217.pub2.](https://pubmed.ncbi.nlm.nih.gov/41705996/)PMID: 36321557Free PMC article.Updated. * [ Intravenous lipid emulsion to reverse acute drug toxicity in pediatric patients. ](https://pubmed.ncbi.nlm.nih.gov/23613099/) Presley JD, Chyka PA.Presley JD, et al.Ann Pharmacother. 2013 May;47(5):735-43. doi: 10.1345/aph.1R666. 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Epub 2011 Oct 24.Anesth Analg. 2012.PMID: 22025489 * [ An _in vitro_ study to determine the impact of lipid emulsion on partitioning of a broad spectrum of drugs associated with overdose. ](https://pubmed.ncbi.nlm.nih.gov/38966589/) Barker K, Stewart M, Rutter A, Whitfield PD, Megson IL.Barker K, et al.BJA Open. 2024 Jun 12;10:100292. doi: 10.1016/j.bjao.2024.100292. eCollection 2024 Jun.BJA Open. 2024.PMID: 38966589Free PMC article. * [ What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient? ](https://pubmed.ncbi.nlm.nih.gov/25634667/) Lee HM, Archer JR, Dargan PI, Wood DM.Lee HM, et al.Clin Toxicol (Phila). 2015 Mar;53(3):145-50. doi: 10.3109/15563650.2015.1004582. Epub 2015 Jan 29.Clin Toxicol (Phila). 2015.PMID: 25634667Review. 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