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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Clinical pharmacokinetics of meropenem and biapenem in bile and dosing considerations for biliary tract infections based on site-specific pharmacodynamic target attainment.
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Clinical pharmacokinetics of meropenem and biapenem in bile and dosing considerations for biliary tract infections based on site-specific pharmacodynamic target attainment.

机译：美罗培南和比阿培南在胆汁中的临床药代动力学以及基于特定部位药效学目标实现胆道感染的剂量注意事项。

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摘要

The present study investigated the pharmacokinetics of meropenem and biapenem in bile and estimated their pharmacodynamic target attainment at the site. Meropenem (0.5 g) or biapenem (0.3 g) was administered to surgery patients (n = 8 for each drug). Venous blood samples and hepatobiliary tract bile samples were obtained at the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo simulation to predict the probability of attaining the pharmacodynamic target (40% of the time above the MIC). Both drugs penetrated similarly into bile, with mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to 0.38 (area under the drug concentration-time curve). The usual regimens of meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions) achieved similar target attainment probabilities in bile (>/= 90%) against Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae isolates. However, against Pseudomonas aeruginosa isolates, meropenem at 1 g q8h and biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively. The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target attainment probability in bile was >/= 90%) was 1 mg/liter for 0.5 g q8h and 2 mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter for 0.6 g q8h for biapenem. These results help to define the clinical pharmacokinetics of the two carbapenems in bile while also helping to rationalize and optimize the dosing regimens for biliary tract infections based on site-specific pharmacodynamic target attainment.
机译：本研究调查了美罗培南和比阿培南在胆汁中的药代动力学，并估计了它们在该部位的药效学目标。美罗培南（0.5 g）或比阿培南（0.3 g）被施用于手术患者（每种药物n = 8）。在输注结束时（0.5 h）并在此后最多5 h内获得静脉血样本和肝胆道胆汁样本。药代动力学分析血浆和胆汁中的药物浓度，并将其用于蒙特卡洛模拟，以预测达到药效学指标的可能性（高于MIC的时间的40％）。两种药物都类似地渗入胆汁，平均胆汁/血浆比率为0.24至0.25（最大药物浓度）和0.30至0.38（药物浓度-时间曲线下的面积）。美罗培南（每8小时[q8h]每0.5克）和比阿培南（0.5小时每h输注0.5h）的常用方案在针对大肠杆菌，肺炎克雷伯菌和阴沟肠杆菌分离株。但是，对于铜绿假单胞菌分离株，分别需要美罗培南在1 g q8h和比阿培南在0.6 g q8h的值分别为80.7％和71.9％。基于胆道药效学的断点（胆汁中目标达到概率> / = 90％的最高MIC）对于美罗培南和0.5 mg /升，0.5 g q8h为1 mg / l，1 g q8h为2 mg / l对于比阿培南，每克0.3克q8h的剂量为1毫克/升，对于每克0.6克q8h剂量的0.6毫克/升。这些结果有助于确定胆汁中两种碳青霉烯类的临床药代动力学，同时还有助于根据特定部位的药效学目标达成合理化和优化胆道感染的给药方案。

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