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Local anesthetics in lipid-depot formulations--neurotoxicity in relation to duration of effect in a rat model
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- Dyhre, Henrik (author)
- Lund University,Lunds universitet,Anestesiologi och intensivvård,Forskargrupper vid Lunds universitet,Anaesthesiology and Intensive Care Medicine,Lund University Research Groups
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- Söderberg, Lars (author)
- Lund University,Lunds universitet,Livsmedelsteknik,Avdelningen för livsmedel och läkemedel,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Food Technology, Engineering and Nutrition,Division of Food and Pharma,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH
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- Björkman, Sven (author)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Hammarlund-Udenaes
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- (creator_code:org_t)
- BMJ, 2006
- 2006
- English.
- In: Regional anesthesia and pain medicine. - : BMJ. - 1098-7339 .- 1532-8651. ; 31:5, s. 401-408
- Journal article (peer-reviewed)
Abstract
Subject headings
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- BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the possible local neurotoxicity of a number of lipid-depot formulations of local anesthetics in relation to their duration of action in sciatic-nerve block. METHODS: Formulations that contain 2%, 4%, 8%, 16%, 32%, or 64% of a mixture of bupivacaine and lidocaine base 4:1 in medium-chain triglyceride were prepared and evaluated, together with 0.5%, 1.0%, and 2.0% bupivacaine HCl solutions, bupivacaine 4.2% or 7.0% in medium-chain triglyceride, and 20% lidocaine base in a polar lipid vehicle. The duration of sensory and motor sciatic-nerve block was determined in rats. A week later, the sciatic nerves were dissected and removed for histopathologic examination by light microscopy. RESULTS: The duration of sensory and motor-nerve block was prolonged almost 4 times with the 32% and 13 times with the 64% bupivacaine:lidocaine formulation, in comparison to the 0.5% aqueous solution. The 64% formulation was applied by injection and also placed directly on the nerve with similar results. Slight to moderate signs of neurotoxicity were only found after administration of the 64% formulation. CONCLUSIONS: The findings suggest that depot formulations of local anesthetics with advantageous pharmaceutical and pharmacologic properties can be prepared by use of bupivacaine as the active component and natural lipids as carriers. A favorable balance between effects and toxicity may conceivably be obtained. After supplemental testing in more sensitive models for toxicity, such formulations could be candidates for clinical trials.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
Keyword
- Bupivacaine
- Lidocaine
- Local anesthetics
- Neurotoxicity
- Sciatic-nerve block
- MEDICINE
- MEDICIN
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- ref (subject category)
- art (subject category)
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