摘要目的 探讨6种抗菌药物在胆汁中的药物代谢动力学特点,并评估其杀菌效力.方法 实验用健康家兔36只,随机分为6组,每组6只.行胆总管造瘘术后,分别静脉注射头孢曲松、头孢哌酮/舒巴坦钠、哌拉西林/他唑巴坦、美罗培南、左氧氟沙星、甲硝唑,于注射后不同时间收集家兔胆汁标本,采用高效液相色谱法测定各抗菌药物的浓度,并计算出药物代谢动力学参数.结合最低抑菌浓度(MIC)评估各抗菌药物在胆汁中的杀菌效力.结果 各抗菌药物在胆汁中的峰浓度和半衰期分别为:哌拉西林(7 950 ±3 023) mg/L和(1.97±1.23)h,头孢曲松(1 104±248) mg/L和(3.14±0.57)h,头孢哌酮(5 215 ±2 225) mg/L和(0.89 ±0.13)h,美罗培南(31.97 ±12.44) mg/L和(0.36±0.11)h,左氧氟沙星(66.3±36.9) mg/L和(3.32±2.57)h,甲硝唑(28.2±10.2) mg/L和(0.81 ±0.33)h.哌拉西林/他唑巴坦和头孢哌酮/舒巴坦的杀菌指数最大,分别为(62.1±23.6) ～(993.8±377.9)和(164.8 ±69.0) ～ (659.3 ±275.9),其药物浓度持续在MIC以上的时间(T＞MIC)最长,两药的T＞MIC分别为(6.00±2.53)～(8.00±0.00)h和(6.33±1.97) ～ (8.00±0.00)h;左氧氟沙星的杀菌指数[(2.1±1.2)～(8.3±4.6)]和T＞MIC[(0.54±0.25)～(2.67±1.03)h]最小,头孢曲松和美罗培南居中,其杀菌指数和T＞MIC分别为(4.3±1.0) ～ (69.2±15.5)、(1.42±0.65)～(8.00±0.00)h和(2.0±0.8)～(1 031.3 ±401.4)、(0.29 ±0.10) ～ (1.83 ±0.26)h.甲硝唑对厌氧菌的杀菌指数和T＞MIC分别为7.4 ～294.9和1.88 ～5.00 h.结论 6种抗菌药物均可在胆汁中达到有效杀菌浓度,哌拉西林、头孢哌酮、美罗培南、甲硝唑在家兔胆汁中呈一房室模型,头孢曲松、左氧氟沙星为二房室模型分布.哌拉西林/他唑巴坦和头孢哌酮/舒巴坦杀菌效力最强,甲硝唑对厌氧菌有较强的杀菌力,肝胆系统感染应结合临床选用杀菌效力强的抗菌药物.

abstractsObjective To study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile,and evaluate their microbicidal potential.Methods Thirty-six health rabbits were randomly divided into 6 groups,and each group was 6 rabbits.After anaesthesia,the common bile duct of rabbit was isolated and cumulated with a silicone tube.The rabbits were administered intravenously with the equal-effect dose of antibiotics.Bile(1.5 ml) was collected at different time points after administration,and the concentration of antibiotics of bile was assayed by high performance liquid chromatography.The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (Cmax),peak time (Tmax),half-life time (T1/2),clearance (CL) and apparent volume of distribution(VD).The bile antibiotics concentration contrasted to the minimum inhibitorv concentration (MIC),and attained the bactericidal index(Cmax/MIC) and the time when the drug concentration exceeded the MIC(T＞MIC).Results The C and T1/2 of each antibiotic were as the followings:piperacillin(7 950 ± 3 023) mg/L and (1.97 ± 1.23) h,ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h,cefoperazone (5 215 ±2 225) mg/Land (0.89±0.13) h,meropenem(31.97 ±12.44) mg/L and (0.36±0.11) h,levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h,metronidazole(28.2 ± 10.2) mg/L and (0.81 ± 0.33) h,respectively.Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T＞MIC,and their bactericidal indexes were (62.1 ±23.6)-(993.8 ±377.9) and(164.8 ± 69.0)-(659.3 ±275.9),their T＞MIC were(6.00±2.53)-(8.00±0.00) b and(6.33 ± 1.97)-(8.00 ±0.00) h.The bactericidal index and T＞MIC of levofloxacin were the smallest,which were (2.1 ± 1.2)-(8.3 ± 4.6) and (0.54 ± 0.25)-(2.67 ± 1.03) h.Ceftriaxone and meropenem were as the medium,and their bactericidal indexes and T ＞ MIC were (4.3 ± 1.0)-(69.2 ± 15.5),(1.42 ± 0.65)-(8.00±0.00) h and (2.0 ±0.8)-(1 031.3 ±401.4),(0.29 ± 0.10)-(1.83 ±0.26) h.The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9,and the T ＞ MIC ranged from 1.88 to 5.00 h.Conclusions The bile concentrations of six antibiotics all exceed their effective bactericidal concentrations.The concentration-time curves of piperacillin,cefoperazone,meropenem and metronidazole conformed to one-compartment model,and ceftriaxone and levofloxacin are conformed to two-compartment model.Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T＞MIC,so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic,the microbicidal potential of metronidazole is high.