Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia
Pharmacokinetic analysis of doripenem in elderly patients with nosocomial pneumonia
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DOI：
10.1016/j.ijantimicag.2013.03.012
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发表时间：
2013-08-01
影响因子：
10.8
通讯作者：
Chida, Kingo
中科院分区：
文献类型：
--
作者：
Harada, Masanori;Inui, Naoki;Chida, Kingo
多利培南是一种具有广谱抗菌活性的注射用碳青霉烯类抗生素。静脉注射1h的药代动力学分析对10例临床确诊的老年医院获得性肺炎(NP)患者给予500 mg多利培南治疗。血浆中未发生变化的多利培南浓度通过与串联质谱仪联用的高效液相色谱检测方法进行测定。多利培南500 mg静脉滴注1h的最大血药浓度、稳态血药浓度-时间曲线下面积、达到最大血药浓度时间和终末消除半衰期的几何均值分别为22.40、57.02、1.0h和1.89h。此外，还进行了群体PK分析，以考察影响多利培南药代动力学的因素，并通过后贝叶斯估计估计超过最小抑菌浓度(T&gT；MIC)的时间。肌酐清除量是影响多利培南清除量的最显著的协变量。在所有患者中，对2微克/毫升MIC的估计%T&>MIC均超过40%。在治疗老年NP患者时，1-h静脉滴注。每日三次，每次500毫克的多利培南对细菌有良好的抗菌作用，最低抑菌浓度可达2微克/毫升，因此可作为治疗非典型肺炎的一种选择。(C)2013年爱思唯尔公司和国际化疗学会。版权所有。
Doripenem is a parenteral carbapenem antibiotic with broad-spectrum antimicrobial activity. A pharmacokinetic (PK) analysis of a 1-h intravenous (i.v.) dose of 500 mg doripenem in ten clinically ill, elderly patients with nosocomial pneumonia (NP) was conducted. Concentrations of unchanged doripenem were measured in plasma using a validated liquid chromatography method coupled to a tandem mass spectrometry assay. Geometric means of maximum plasma concentration, area under the plasma concentration-time curve over the dosing interval at steady state, time to reach maximum plasma concentration, and terminal elimination half-life for 500 mg doripenem as a 1-h infusion were 22.40 mu g/mL, 57.02 mu g h/mL, 1.0 h and 1.89 h, respectively. In addition, a population PK analysis was performed to examine the influencing factors on the pharmacokinetics of doripenem and to estimate the time above minimum inhibitory concentration (T > MIC) by a post hoc Bayesian estimation. The effect of creatinine clearance was the most significant covariate on doripenem clearance. The estimated %T > MIC against a MIC of 2 mu g/mL exceeded 40% in all patients. In the treatment of NP in elderly patients, a 1-h i.v. dose of 500 mg doripenem three times daily may provide a favourable antimicrobial effect against bacteria with MICs up to 2 mu g/mL and would therefore be a treatment option for NP. (c) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.