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

BACKGROUND: 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.

METHODS: After administration of intravenous infusion of bupivacaine at 2 mg·kg·min 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·min 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.

RESULTS: In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group.

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