| Safety and pharmacokinetics of an endotoxin-binding phospholipid emulsion. | |
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MedLine Citation:
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PMID: 12841798 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Lipids and lipoproteins have been shown to bind and neutralize endotoxin and to improve outcomes in animal models of sepsis. OBJECTIVE: To provide safety and pharmacokinetic data for a protein-free, phospholipid-rich emulsion developed as an agent to neutralize endotoxin, and to study the changes in lipids and lipoproteins following emulsion administration. METHODS: Thirty healthy male volunteers (aged 18-45 y) were given an emulsion containing 92.5% soy phospholipid, 7.5% soy triglyceride, and 18 mM sodium cholate using a double-blind, placebo-controlled crossover protocol. Emulsion at 3 escalating doses (75, 150, 300 mg/kg) based on phospholipid content was administered by intravenous infusion over 2 hours in the low- and mid-dose groups and 6 hours in the high-dose group. RESULTS: All subjects completed the protocol without significant toxicities. A slight dose-dependent increase in indirect bilirubin at the 24-hour time point was observed in the emulsion treatment period, with a maximum difference between placebo and emulsion of 0.9 mg/dL. Mean +/- SD peak phospholipid levels were 316 +/- 30, 533 +/- 53, and 709 +/- 86 mg/dL, and phospholipid half-lives were 5.4 +/- 0.6, 5.4 +/- 0.5, and 8.0 +/- 0.8 hours for the low, mid, and high doses, respectively. Increases in total cholesterol, low-density lipoprotein cholesterol and apolipoprotein A-I and B levels were observed. High-density lipoprotein cholesterol decreased immediately following emulsion infusion, but rebounded to above placebo levels by 24 hours. CONCLUSIONS: A unique phospholipid-rich emulsion was shown to have a favorable safety profile and to expand the blood lipid and lipoprotein pool without the use of human-derived blood products. Lipid levels expected to protect against the physiologic effects of bacterial endotoxin were achieved. |
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Authors:
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Bruce R Gordon; Thomas S Parker; Daniel M Levine; Stuart D Saal; Lisa Cooper Hudgins; Betty-Jane Sloan; Cindy Chu; Kurt H Stenzel; Albert L Rubin |
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Publication Detail:
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Type: Clinical Trial; Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Annals of pharmacotherapy Volume: 37 ISSN: 1060-0280 ISO Abbreviation: Ann Pharmacother Publication Date: 2003 Jul-Aug |
Date Detail:
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Created Date: 2003-07-04 Completed Date: 2003-09-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9203131 Medline TA: Ann Pharmacother Country: United States |
Other Details:
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Languages: eng Pagination: 943-50 Citation Subset: IM |
Affiliation:
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The Rogosin Institute, New York, NY 10021-9809, USA. gordobr@mail.rockefeller.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Apolipoproteins / analysis Bile Acids and Salts / analysis Cholic Acids / analysis Cross-Over Studies Dose-Response Relationship, Drug Double-Blind Method Endotoxins / metabolism* Fat Emulsions, Intravenous / adverse effects, metabolism*, pharmacokinetics Humans Male Middle Aged Phospholipids / adverse effects, analysis, metabolism*, pharmacokinetics Triglycerides / analysis, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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M01-RR00102/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins; 0/Bile Acids and Salts; 0/Cholic Acids; 0/Endotoxins; 0/Fat Emulsions, Intravenous; 0/Phospholipids; 0/Triglycerides |
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