Department of Nephrology, Hospital Universitario Ramón y Cajal, Madrid.
Department of Medicine, School of Medicine, Universidad de Alcalá, Alcalá de Henares.
Ther Drug Monit. 2019 Jun;41(3):376-382. doi: 10.1097/FTD.0000000000000595.
An optimal antifungal therapy for invasive candidiasis in critically ill patients is essential to reduce the high mortality rates. Acute kidney injury is common, and continuous renal replacement therapies are frequently used. Previous studies have demonstrated a lack of effect from different continuous renal replacement techniques on micafungin clearance. However, the use of high cutoff pore size membranes could potentially allow for the loss of albumin and alter micafungin pharmacokinetics. The objective was to explore the pharmacokinetics of micafungin in critically ill patients undergoing continuous venovenous high cutoff membrane hemodialysis (CVVHD-HCO).
Prospective observational study performed in critically ill patients treated with 100 mg/d of micafungin and undergoing CVVHD-HCO. CVVHD-HCO sessions were performed using Prisma-Flex monitors and dialyzers with a membrane of polyarylethersulfone of 1.1-m surface area and 45-kDa pore size. Blood samples were collected from arterial prefilter, venous postfilter, and the drainage line ports at 0 (predose), 1, 4, 12, 24 hours after dose, and micafungin concentrations were determined using HPLC-UV.
Nine patients (55.6% male; age: 28-80 years) were included. Median (range) of micafungin concentrations in the effluent were <0.2 (<0.2-0.4) mg/L at low (predose) and 0.4 (<0.2-0.7) mg/L at high (1 h) concentrations. The extraction ratio was <12% at each time point. A 2-compartment model best described the time course of plasma concentrations, and body weight was the only covariate that improved the model.
This is the first study demonstrating that CVVHD-HCO does not alter the pharmacokinetics of micafungin, and that standard doses of this antifungal can be used.
对于重症患者侵袭性念珠菌病，优化的抗真菌治疗对于降低高死亡率至关重要。急性肾损伤很常见，经常使用连续肾脏替代疗法。先前的研究表明，不同的连续肾脏替代技术对米卡芬净清除率没有影响。然而，使用高截止孔径膜可能会导致白蛋白丢失并改变米卡芬净的药代动力学。目的是探讨重症患者接受连续静脉-静脉高截止膜血液透析（CVVHD-HCO）时米卡芬净的药代动力学。
前瞻性观察研究纳入了接受 100mg/d 米卡芬净治疗并接受 CVVHD-HCO 的重症患者。使用 Prisma-Flex 监测仪和聚芳醚砜膜（表面积为 1.1m2，孔径为 45kDa）的透析器进行 CVVHD-HCO 治疗。在给药前（0 小时）、给药后 1、4、12 和 24 小时，从动脉预滤器、静脉后滤器和引流管路端口采集血样，并使用 HPLC-UV 测定米卡芬净浓度。
共纳入 9 例患者（55.6%为男性；年龄：28-80 岁）。低（给药前）和高（1 小时）浓度时，米卡芬净在流出液中的中位数（范围）浓度分别为<0.2（<0.2-0.4）mg/L 和 0.4（<0.2-0.7）mg/L。各时间点的提取率均<12%。双室模型最能描述血浆浓度的时间过程，体重是唯一能改善模型的协变量。
这是第一项表明 CVVHD-HCO 不会改变米卡芬净药代动力学的研究，表明可以使用该抗真菌药物的标准剂量。
