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The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride

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Lipid infusions have been proposed to treat local anesthetic–induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model.


After administration of intravenous infusion of bupivacaine at 2 mg·kg−1·min−1 for 5 minutes in Sprague–Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg−1·min−1 for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography–tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics.


In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min−1·kg−1, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg−1, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min−1, P = .021, P′ = .032) were larger; and the area under the blood concentration–time curve 0 − t; (605 ± 82 vs 867 ± 110 mgL−1·min−1, P =.001) and the area under the blood concentration–time curve (0 − ∞) (697 ± 111 vs 991 ± 121 mgL−1·min−1, P =.001) were less, when compared with the LCT/MCT group.


LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.
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Document Type: Research Article

Publication date: November 1, 2016

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