• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Drugs and aging >Pharmacokinetics and pharmacodynamics of meropenem in elderly chinese with lower respiratory tract infections: population pharmacokinetics analysis using nonlinear mixed-effects modelling and clinical pharmacodynamics study.
【24h】

Pharmacokinetics and pharmacodynamics of meropenem in elderly chinese with lower respiratory tract infections: population pharmacokinetics analysis using nonlinear mixed-effects modelling and clinical pharmacodynamics study.

机译：美洛培南在老年人下呼吸道感染中的药代动力学和药效学：使用非线性混合效应模型进行人群药代动力学分析和临床药效学研究。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly. OBJECTIVE: The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients. METHODS: We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM(R)) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (AUC/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (Cmin/MIC) were analysed for their association with clinical and bacteriological outcomes. RESULTS: A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63-95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CLCR) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram-negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p<0.05). However, logistic regression analysis showed that only %T>MIC independently influenced clinical outcome (p=0.001, odds ratio [OR]=1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p<0.05). Logistic regression analysis showed that %T>MIC (p=0.008, OR=1.047) and serum level of albumin (p=0.033, OR=1.434) independently influenced bacteriological eradication. CONCLUSIONS: To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CLCR and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success.
机译：背景：美罗培南是一种广谱抗菌剂，通常用于治疗严重的下呼吸道感染（LRTIs）。然而，缺乏公开的研究来探讨美洛培南的人群药代动力学，该药的临床药效学和中国LRTI患者，特别是老年人对药物反应的相关性。目的：本研究的目的是利用患者数据建立美洛培南的药代动力学模型，并探讨美洛培南在中国老年LRTI患者中的临床药效学。方法：我们分别在每8或12小时内接受0.5小时输注美罗培南0.5或1.0 g的患者中，测定其血清美罗培南的浓度。美洛培南的药代动力学分析是使用非线性混合效应模型（NONMEM®）软件进行的。美洛培南对革兰氏阴性杆菌的最低抑菌浓度（MIC）通过E检验法进行了测试。高于MIC的时间百分比（％T> MIC），血清浓度-时间曲线下的药物面积与MIC的比值（AUC / MIC），药物的最大血清浓度与MIC的比值（ Cmax / MIC）以及药物与MIC的最低血清浓度之比（Cmin / MIC）与临床和细菌学结果之间的关系进行了分析。结果：从75名患者（年龄63-95岁）中获得了284种血清美罗培南的浓度测量值。两室模型最适合浓度数据。协变量肌酐清除率（CLCR）和急性生理与慢性健康评估（APACHE）II评分对美罗培南的药代动力学影响最大。共有45名患者参加了药效学研究，其中包括25名临床应答者和21名消灭细菌的患者。 45例患者均从气管吸出物或痰中分离出革兰阴性杆菌。 25名临床缓解者的％T> MIC，AUC / MIC，Cmax / MIC和Cmin / MIC值显着高于无缓解者（所有p <0.05）。但是，逻辑回归分析表明，只有％T> MIC独立地影响临床结果（p = 0.001，优势比[OR] = 1.065）。使用％T> MIC预测临床成功的临界值为76％; ％T> MIC预测成功应答的敏感性和特异性分别为84％和85％。 21例细菌学消灭患者的％T> MIC，AUC / MIC，Cmax / MIC和Cmin / MIC值以及血清白蛋白水平显着高于细菌治疗失败的患者（所有p <0.05） 。 Logistic回归分析表明，％T> MIC（p = 0.008，OR = 1.047）和血清白蛋白水平（p = 0.033，OR = 1.434）独立影响细菌的根除。结论：据我们所知，这是首次研究美洛培南在老年人中的群体药代动力学和临床药效学。 CLCR和APACHE II评分对美罗培南的药代动力学有重要影响。在LRTI患者中，％T> MIC的76％的临界值可用于优化美罗培南剂量方案，以取得临床成功。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号