Distribution and Concentration of Meropenem in Rabbit Bile_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHENG Jinglei , LIANG Lijian , PENG Baogang , LI Shaoqiang , HUA Yunpeng

Department of Hepatobiliary Surgery， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China;

Corresponding author：

Keywords：

Meropenem; Bile; Concentration; High performance liquid chromatography

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Objective 　To study the distribution and concentration of meropenem in rabbit bile.
Methods 　The rabbits were cannulated with a silicone tube in the common bile duct and the blank bile was collected. The rabbits were then administered intravenously with meropenem. Multiple bile samples (1.5 ml) were collected at different phases after the administrations. According to requirement of the high performance liquid chromatography (HPLC), the specificity test was undertook. The blank bile was then mixed with meropenem and mobile phase, respectively, in order to obtain a series of bile samples at different concentrations ranging from 0.5 to 500 μg/ml. The samples were analyzed with HPLC and the chromatographic peak area of meropenem contents were quantitated through external reference method. The linear regression equation was used to analyzed the relationship between the drug concentrations and the chromatographic peak areas. The bile samples that were collected after drug administrations were pretreated and the chromatographic peak areas were assayed by the liquid chromatograph. The bile concentrations were then calculated according to the regression equation, and the concentration-time distribution of meropenem in the bile was obtained ultimately.
Results 　The specificity test indicated the bile dopant peak and the meropenem chromatographic peak were well-separated under chromatographic condition of the mobile phase. The standard curve regression equation was S=2 209.10C-1 251.34, r=0.999 9, and minimum quantitation limit of meropenem was 0.5 μg/ml. After a single i.v. administration of 75 mg/kg of meropenem in each rabbit, drug concentrations reached (38.36±14.17) μg/ml immediately in bile， which significantly exceeded the minimum inhibitory concentrations (MIC90) for most gram negatives, which range from 0.031 to 2 μg/ml. The bile concentration of meropenem decreased quickly over time, and meropenem was eliminated completely in rabbit bile 3 hours after intravenous injection.
Conclusion 　Meropenem could achieve adequate bile concentration for the treatment of biliary tract infection due to susceptible bacteria. However, because of its rapid biliary elimination, meropenem should be used in shorter interval time.

Citation： ZHENG Jinglei,LIANG Lijian,PENG Baogang,LI Shaoqiang,HUA Yunpeng. Distribution and Concentration of Meropenem in Rabbit Bile. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(2): 177-180. doi: Copy

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1. 　林洪远，邹声泉，董家鸿，等. 应用抗菌药物防治外科感染的指导意见Ⅷ [J]. 中华外科杂志， 2004； 42（2）∶117.
2. 　Sheen-Chen S, Chen W, Eng H, et al. Bacteriology and antimicrobial choice in hepatolithiasis [J]. Am J Infect Control， 2000; 28(4)∶298.
3. 　黄美雄，唐大年，李波，等. 奈替米星在血、胆囊组织及尿液中的分布 [J]. 中华肝胆外科杂志， 1999； 5（2）∶109.
4. 　郑惊雷，梁力建，赖佳明. 胆道感染病原菌及其对抗生素敏感性变化的研究 [J]. 中国实用外科杂志， 2005； 25（2）∶86.
5. 　葛庆华，吴卫泽，支晓瑾，等. 头孢曲松(罗氏芬)在T-管胆汁中药动学研究 [J]. 中华肝胆外科杂志， 2004； 10（1）∶23.
6. 　黎沾良，邓群，陆连荣，等. 抗生素对肝脏和胰腺组织穿透能力及杀菌效力的实验研究 [J]. 中华外科杂志， 1998； 36（增刊）∶44.
7. 　Mendez AS, Weisheimer V, Oppe TP, et al. Microbiological assay for the determination of meropenem in pharmaceutical dosage form [J]. J Pharm Biomed Anal， 2005; 37(4)∶649.
8. 　殷果, 李玉兰, 邓颖, 等. 旋光法测定注射用美罗培南的含量 [J]. 医药导报， 2004； 23（11）∶865.
9. 　Mrestani Y, Neubert R, Nagel F. Capillary zone electrophoresis determination of meropenem in biological media using a high sensitivity cell [J]. J Pharm Biomed Anal， 1999; 20(6)∶899.
10. 　Robatel C, Buclin T, Eckert P, et al. Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC [J]. J Pharm Biomed Anal， 2002; 29(1-2)∶17.
11. 　徐叔云，卞如濂，陈修主编. 药理实验方法学 [M]. 第3版. 北京：人民卫生出版社， 2002∶740～742.
12. 　李家泰，李耘，　齐慧敏.　 2002-2003年中国革兰阴性细菌耐药性监测研究 [J]. 中华检验医学杂志, 　2005；　 28(1)∶16.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Distribution and Concentration of Meropenem in Rabbit Bile

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