美罗培南在成人脓毒症或脓毒性休克患者中的群体药动学研究综述

Population pharmacokinetics of meropenem:A review in adult patients with sepsis or septic shock

目的 本综述旨在提供已报道的美罗培南在成人脓毒症或脓毒性休克患者中的群体药动学(population pharmacokinetics,PopPK)模型,并确定使这类患者药动学变化的协变量因素,以发现美罗培南在该类患者PopPK研究中的新靶点。方法 在PubMed和Medline数据库中检索了2012年1月至2023年3月期间发表的美罗培南在脓毒症或脓毒性休克患者中的PopPK研究,并对相关参考文献进行了筛查。结果 该检索共产生12项符合纳入条件的研究,一室和二室模型分别在3项和8项研究中被报道为能最好地描述美罗培南的PopPK。40多个协变量被纳入筛选,最常见的协变量因素是肌酐清除率和体重,年龄是次要协变量因素。美罗培南清除率和总表观分布容积的估计值分别在1.5~14.1 L/h和11.3~39.7 L范围内变化较大。半数以上研究均采用指数模型作为基础模型。结论 首先,本文强调了对该类患者估计的PopPK参数的宽泛性和可变性,并提供影响该类患者清除率和表观分布容积的协变量因素;其次,正如大多数研究报道那样,延长输注时间以及应用治疗药物监测似乎是多数研究报道的维持有效浓度在抑菌浓度之上较好的方法,但还需进一步研究以得到可靠结论。这些信息均有助于指导该类患者的给药。

Objective This study developed a population pharmacokinetic(PopPK) model of meropenem in adult patients with sepsis or septic shock.It identified the factors that influence changes in the drug's pharmacokinetics in these individuals.The aim was to explore a new target for meropenem in PopPK studies including this patient group.Methods PopPK studies of meropenem in patients with sepsis or septic shock published from January 2012to March 2023 were found in the PubMed and Medline databases,and relevant references were screened.Results In total,12 studies were deemed eligible for this review,and the one-and two-compartment models were reported to best describe the PopPK of meropenem in three and eight studies,respectively.More than 40 covariates were screened;the most common covariates were creatinine clearance and body weight,with age acting as a secondary factor.The estimated values of the clearance rate and total apparent distribution volume of meropenem varied greatly in the range of 1.5~14.1 L/h and 11.3~39.7 L,respectively.More than 50% of the studies applied the exponential model.Conclusion This review emphasized the extensiveness and variability of PopPK parameters estimated for this population and provided covariates that affected clearance and the apparent volume of distribution in this patient group.Second,prolonged infusion time and therapeutic drug monitoring seemed more suited for maintaining effective inhibitory concentrations,as widely reported,although further studies were warranted to draw reliable conclusions.The cumulative information obtained from this review could guide the drug administration system in this population.