Abstract
Objective To study the concentrations and pharmacokinetics of beta-lactams antibi-otics in rabbit bile and evaluate their microbicidal potential to present theoretical evidence and reference for choosing effective antibiotics for the prevention and therapy of hepatobiliary infection. Methods After anesthesia, the common bile duct of rabbits was isolated and cannulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of beta-lactams antibiotics. Bile (1.5 ml) was collected at the time of 0. 25,0.5,0. 75,1,1.5,2,3,4,6,8 h after administration and as-sayed by HPLC. 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 concen-tration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (Cmax/MIC) and the time the drug concentration exceeded the MIC (TMIC) to evaluate microbicidal potential of the antibiotics in bile. Results The Cmax and T1/2 of each antibiotic were as follow: pip-eracillin (7950.16±3023.00)μg/ml and (1.97±1.23) h, ceftriaxone (1107.01±247.61)μg/ml and (3.14±0. 57)h,meropenem (31.97±12.44)μg/ml and (0. 36±0. 11)h. Piperacillin/tazobactam had the largest bactericidal index and the longest TMIC, and it can form 100 times of concentration than the MIC90 of the common pathogens in bile. Also its TMIC maintained 5~8 h. The bactericidal index and TMIC of ceftriaxone and meropenem were smaller as contrasted to the former. Conclusions The bile concentrations of three antibiotics all exceed their effective bactericidal concentrations. Piperacil-lin/tazobactam has the largest bactericidal index and the longest TMIC, so it can be of the first choice for the therapy in hepatobiliary infection. Key words: Antibiotics; Bile; Pharmacokinetics; Microbicidal potential; HPLC
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