脂肪乳剂对布比卡因药代动力学的影响  

Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine

作　　者：罗中兵[1] 张燕辉[1] 陶军[1] 宋晓阳[1] 李文献[2] 

机构地区：[1]广州军区武汉总医院麻醉科,湖北武汉430070 [2]复旦大学附属眼耳鼻喉医院麻醉科

出　　处：《华南国防医学杂志》2013年第12期866-869,共4页Military Medical Journal of South China

摘　　要：目的观察脂肪乳剂对布比卡因药代动力学的影响，探讨脂肪乳剂救治布比卡因中毒的主要机制。方法14只新西兰大白兔随机分对照组和实验组2组，每组7只（n=7）。2组实验动物均在3rain内静脉持续注射布比卡因2mg／kg后，对照组在7rain内持续静脉输注生理盐水15ml／kg，而实验组输注20％英脱利匹特（长链脂肪乳剂）15ml／kg。布比卡因开始输注后60min内，使用高效液相技术在第3min和每10min测定每组实验动物血浆布比卡因浓度，以及第65min时的心肌布比卡因的浓度。记录平均动脉压（mean arterial pressure，MAP）、心率（heart rate，HR）和心电图（electrocardiogram，ECG）等的变化，计算药代动力学参数。结果布比卡因开始输注后第10-60min内，每10min测定的MAP、HR，组内和基础值比较，以及组间比较差异均无统计学意义（P〉0．05）。布比卡因开始输注后第3min时，实验组和对照组血浆布比卡因浓度差异无统计学意义（P〉0．05），而在其它相同时间点的血浆布比卡因浓度，实验组均显著高于对照组（P〈0．01）。对照组房室参数t1/2β、V1、CL等均高于实验组，而AUC、K10、K21，等均低于实验组（P〈0．05），t1／2α和K12差异无统计学意义（P〉0．05）；对照组统计矩参数AUC（0-t）和AUC（0-∞）均低于实验组，而Vz和CLz均高于实验组，MRT（0-t）和t1／2z差异无统计学意义（P〉0．05）；对照组心肌布比卡因浓度为（304±61）ng／g显著高于实验组（176±50）ng／g（P〈0．01）。结论脂肪乳剂输注后提高布比卡因血浆药物浓度，降低心脏组织中的布比卡因药物浓度，“脂肪池机制”可能是脂肪乳剂救治局麻药中毒的主要机制。Objective To observe the effect of lipid emulsion on the pharmaeokineties of bupivaeaine and explore main treatment mechanisms of lipid emulsion on bupivaeaine poisoning. Methods Fourteen New Zealand white rabbits were randomly divided into 2 groups：control group （group I ） and experimental group （group II ） （n = 7 each）. All experimental animals were injected with bupivaeaine 2 mg/kg in 3 minutes, then group I was infused with normal saline 15 ml/kg and group U was infused with 20% Intralipid 15 ml/kg in 7 minutes. After the started injection of bupivaeaine, Plasma bupivacaine concentration was measured at 3 minutes and every 10 minutes in 60 minutes with high performance liquid chromatography （HPLC）, and myocardial bupivacaine concentrations were measured at 65 minutes in 2 groups. Mean arterial pressure （MAP）,heart rate （HR） and electrocardiogram （ECG） changes were recorded. The pharmacokinetic parameters were calculated. Results MAP, HR, ECG and plasma bupivacaine concentration at 3 minutes were not significantly different in 2 groups （P〉0. 05）. The plasma bupivacaine concentrations at the same time point every 10 minutes in group II were significantly higher than group I （P〈0. 01）. The CL, t1/2β,V1,Vz and CL in group I were higher than in group III （P〈0. 05）. The AUC,Klo ,K21 ,AUC （0-t） and AUC （0-∞）in group I were lower than in group II （P 〈0. 05）. The t1/2. and K12 were not statistically significantly different in 2 groups （P〉0. 05）. Myocardial bupivacaine concentration in group I was （304 ± 61） ng/g which was significantly higher than （176 ± 50） ng/g in group II （P〈0. 01）. Conclusion The lipid emulsion could increase bupivacaine concentration in plasma and reduce its concentration in the heart tissue. The possible main mechanism that lipid emulsion can reduce cardiac toxicity of bupivacaine is ＂lipid pool＂ effect.

关 键 词：布比卡因 英脱利匹特 脂肪乳剂 局麻药 药代动力学 高效液相 

分 类 号：R614.3[医药卫生—麻醉学]