title: The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.
abstract: BACKGROUND
  While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine.
  
  
  METHODS
  Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg(-1)·min(-1) for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg(-1)·min(-1) for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine.
  
  
  RESULTS
  All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2β of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg(-1)·kg(-1) vs 9 ± 4 mL·mg(-1)·kg(-1), P = 0.038), and the t1/2α was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes.
  
  
  CONCLUSIONS
  The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.
authors: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical College, Zhejiang, China.
authors: Kejian
authors: K
authors: Shi
authors: Yun
authors: Y
authors: Xia
authors: Quanguang
authors: Q
authors: Wang
authors: Yiquan
authors: Y
authors: Wu
authors: Xiaoxi
authors: X
authors: Dong
authors: Chanjuan
authors: C
authors: Chen
authors: Wan
authors: W
authors: Tang
authors: Yujian
authors: Y
authors: Zhang
authors: Mengxu
authors: M
authors: Luo
authors: Xianqin
authors: X
authors: Wang
authors: Thomas J
authors: TJ
authors: Papadimos
authors: Xuzhong
authors: X
authors: Xu
mesh_terms: D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000493:pharmacokinetics*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015233:Models, Statistical; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D002045:Bupivacaine