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In vitro and in vivo entrapment of bupivacaine by lipid dispersions.

著者 Litonius E , Lokajova J , Yohannes G , Neuvonen PJ , Holopainen JM , Rosenberg PH , Wiedmer SK
J Chromatogr A.2012 Jul 11 ; ():.
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Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital and University of Helsinki, Finland.

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Intravenous lipid emulsion is recommended as treatment for local anesthetic intoxication based on the hypothesis that the lipophilic drug is entrapped by the lipid phase created in plasma. We compared a 15.6mM 80/20mol% phosphatidyl choline (PC)/phosphatidyl glycerol (PG)-based liposome dispersion with the commercially available Intralipid(®) emulsion in a pig model of local anesthetic intoxication. Bupivacaine-lipid interactions were studied by electrokinetic capillary chromatography. Multilamellar vesicles were used in the first in vivo experiment series. This series was interrupted when the liposome dispersion was discovered to cause cardiovascular collapse. The toxicity was decreased by an optimized sonication of the 50% diluted liposome dispersion (7.8mM). Twenty anesthetized pigs were then infused with either sonicated PC/PG liposome dispersion or Intralipid(®), following infusion of a toxic dose of bupivacaine which decreased the mean arterial pressure by 50% from baseline. Bupivacaine concentrations were quantified in blood samples using liquid chromatography/mass spectrometry. No significant difference in the context-sensitive plasma half-life of bupivacaine was detected (p=0.932). After 30min of lipid infusion, the bupivacaine concentration was 8.2±1.5mg/L in the PC/PG group and 7.8±1.8mg/L in the Intralipid(®) group, with no difference between groups (p=0.591). No difference in hemodynamic recovery was detected between groups (p>0.05).
PMID: 22832037 [PubMed - as supplied by publisher]
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