Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia
Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia.
J Antimicrob Chemother. 2014 Sep;69(9):2508-16. doi: 10.1093/jac/dku177. Epub 2014 May 30.
Doripenem is a newer carbapenem with little data available to guide effective dosing during renal replacement therapy in critically ill patients. The objective of this study was to determine the population pharmacokinetics of doripenem in critically ill patients undergoing continuous venovenous haemodiafiltration (CVVHDF) for acute kidney injury (AKI).
This was an observational pharmacokinetic study in 12 infected critically ill adult patients with AKI undergoing CVVHDF and receiving 500 mg of doripenem intravenously every 8 h as a 60 min infusion. Serial blood samples were taken on 2 days of treatment and used for population pharmacokinetic analysis with S-ADAPT.
The median (IQR) age was 62 (53-71) years, the median (IQR) weight was 77 (67-96) kg and the median (IQR) APACHE II score was 29 (19-32). The median blood, dialysate and replacement fluid rates were 200, 1000 and 1000 mL/h, respectively. A two-compartment linear model with doripenem clearance described by CVVHDF, renal or non-renal mechanisms was most appropriate. The mean value for total doripenem clearance was 4.46 L/h and volume of distribution was 38.0 L. Doripenem clearance by CVVHDF was significantly correlated with the replacement fluid flow rate and accounted for ∼30%-37% of total clearance. A dose of 500 mg intravenously every 8 h achieved favourable pharmacokinetic/pharmacodynamics for all patients up to an MIC of 4 mg/L.
This is the first paper describing the pharmacokinetics/pharmacodynamics of doripenem in critically ill patients with AKI receiving CVVHDF. A dose of 500 mg intravenously every 8 h was appropriate for our CVVHDF settings for infections caused by susceptible bacteria.
多利培南是一种新型碳青霉烯类抗生素，在接受肾脏替代治疗的危重症患者中，其用于急性肾损伤（AKI）的有效剂量的数据有限。本研究的目的是确定接受连续性静脉-静脉血液滤过透析（CVVHDF）治疗 AKI 的危重症患者中多利培南的群体药代动力学。
这是一项观察性药代动力学研究，纳入 12 例接受 CVVHDF 治疗的 AKI 感染性危重症成年患者，接受多利培南 500mg 静脉滴注，每 8 小时 1 次，滴注时间为 60 分钟。在治疗的第 2 天采集系列血样，用于 S-ADAPT 群体药代动力学分析。
中位（IQR）年龄为 62（53-71）岁，中位（IQR）体重为 77（67-96）kg，中位（IQR）急性生理与慢性健康评分Ⅱ（APACHEⅡ）评分为 29（19-32）。中位血液、透析液和置换液流速分别为 200、1000 和 1000mL/h。CVVHDF、肾或非肾机制描述的多利培南清除的两室线性模型最适合。总多利培南清除率的平均值为 4.46L/h，分布容积为 38.0L。CVVHDF 清除率与置换液流速显著相关，占总清除率的 30%-37%。对于所有患者，500mg 静脉滴注，每 8 小时 1 次的剂量，在 MIC 为 4mg/L 时可达到良好的药代动力学/药效学。
这是第一篇描述接受 CVVHDF 治疗的 AKI 危重症患者中多利培南药代动力学/药效学的论文。在我们的 CVVHDF 设置下，对于敏感菌引起的感染，500mg 静脉滴注，每 8 小时 1 次的剂量是合适的。
