title: [Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential].
abstract: OBJECTIVE
  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 (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)).
  
  
  RESULTS
  The C(max) 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/L and (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) h 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.
authors.affiliation: Oncosurgery Department, Dongguan People's Hospital,Dongguan 523059, China. Email: jlzheng@126.com.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Zheng
authors.forename: Lijian
authors.initials: L
authors.lastname: Liang
authors.forename: Zaiguo
authors.initials: Z
authors.lastname: Wang
authors.forename: Baogang
authors.initials: B
authors.lastname: Peng
authors.forename: Shaoqiang
authors.initials: S
authors.lastname: Li
authors.forename: Jiaming
authors.initials: J
authors.lastname: Lai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry* / Q000187:drug effects*; D002438:Cefoperazone / Q000032:analysis / Q000493:pharmacokinetics; D004338:Drug Combinations; D000077731:Meropenem; D008795:Metronidazole / Q000032:analysis / Q000493:pharmacokinetics; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics; D010878:Piperacillin / Q000032:analysis / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011817:Rabbits; D011897:Random Allocation; D013407:Sulbactam / Q000032:analysis / Q000493:pharmacokinetics; D013845:Thienamycins / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013845:Thienamycins; D008795:Metronidazole; D000077725:Piperacillin, Tazobactam Drug Combination; D002438:Cefoperazone; D010397:Penicillanic Acid; D000077731:Meropenem; D013407:Sulbactam; D010878:Piperacillin