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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units
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Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units

机译：人口药代动力学和蒙特卡罗在重症监护单位重症监护单位严重脓毒症早期患者早期术穗病患者的早期蛋白尿模拟

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摘要

Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT(>MIC)) and 80% fT(>MIC). The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 mu g/ml, the PTAs of 40% fT(>MIC) following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 mu g/ml in immunocompromised hosts, the PTAs of 80% fT(>MIC) following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that the V of meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population.
机译：在严重脓毒症早期的早期阶段的病理生理学变化，患有患者的严重脓毒症和脓毒症休克，导致抗生素的药代动力学（PK）模式改变，是影响治疗成功的重要因素。本研究的目的是（i）揭示人口PK参数和（ii）以评估梅洛涅姆的目标成就（PTA）的可能性。在九个患者的第一个24小时内每8小时施用1g梅洛涅姆，在九个患者中进行每8小时进行PK研究，并进行蒙特卡罗模拟以确定在此期间实现40％的曝光时间的PTA游离等离子体药物浓度仍然高于MIC（Ft（> MIC））和80％Ft（> MIC）。这些患者中梅洛涅姆的分布（V）和全部间隙（Cl）分别为23.7升和7.82升/ h。对于4μg/ ml的麦克风的病原体，每8小时施用70％Ft（>麦克风）的PTA为1-H输注，每8小时为4-H次输注0.5克分别为92.52％和90.29％。对于免疫宿主中2μg/ ml的麦克风的病原体，每8小时施用1-H和4-H百分之一的4-H和4-H输注后80％Ft（> MIC）的PTA为84.32％和94.72％，分别。这些发现表明，梅洛涅姆的v较大，梅洛宁的CL低于与健康受试者在先前研究中获得的值。可能需要最大推荐剂量，即每8小时，每8小时2g梅洛芬，治疗该患者人群的危及生命的感染。

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