哌拉西林他唑巴坦在重症患者的肺组织渗透性

Pulmonary penetration in critically ill patients with piperacillin and tazobactam

摘要:

目的  研究重症患者哌拉西林和他唑巴坦的肺通透性，并分析影响药物渗透性的相关因素。方法  对重症患者使用标准剂量哌拉西林他唑巴坦后血浆和肺组织内的药代动力学（PK）进行研究。建立群体药动学模型分析血浆和肺内哌拉西林、他唑巴坦的浓度，主要分析哌拉西林达到药效学评估指标的比例，以及肺通透性对哌拉西林和他唑巴坦肺组织渗透性的影响。结果  哌拉西林和他唑巴坦的平均肺组织渗透率分别为49.3%和121.2%。肺内哌拉西林和他唑巴坦的浓度不足，与肺通透性呈负相关。结论  目前哌拉西林他唑巴坦用于治疗敏感菌感染的重症患者时可能疗效不足。

Abstract:

Objective To quantify the pulmonary penetration of piperacillin and tazobactam in critically ill patients and to investigate factors that may influence the penetration of drug into the lung. Methods The plasma and intrapulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens were studied. A population PK model was developed to describe plasma and intrapulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic end points and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration were explored. Results The median piperacillin and tazobactam pulmonary penetration ratios were 49.3 and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentrations were un-predictable and negatively correlated with pulmonary permeability. Conclusions Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused bypiperacillin-tazobactam-susceptible organisms in some critically ill patients.