Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain
Pharmacy Department, Hospital del Mar, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
J Antimicrob Chemother. 2014 Jun;69(6):1624-32. doi: 10.1093/jac/dku013. Epub 2014 Feb 5.
To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH).
Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions.
Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ± 15.87 versus 71.31 ± 14.24; P = 0.008) and Day 2 (119.01 ± 27.20 versus 104.54 ± 21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis.
There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.
探讨米卡芬净在连续静脉-静脉血液滤过（CVVH）患者中的药代动力学（PK）和药效学（PD）。
纳入 10 名接受 CVVH 治疗且每天给予 100mg 米卡芬净的患者（2012 年 4 月至 12 月）。使用聚醚砜或聚砜血液滤器进行 CVVH。在采样日不更换透析膜。在第 1 天和第 2 天，在输注开始和结束时以及在第 3、5、8、18 和 24 小时，从动脉预滤器和静脉后滤器端口以及超滤液中采集血样。使用 HPLC 测定浓度。计算 AUC0-24 下的浓度-时间曲线下面积（AUC0-24）。使用第 1 天和第 2 天的预滤器和后滤器 AUC0-24/MIC 比值进行蒙特卡罗模拟。使用 AUC0-24/MIC 切点（C. parapsilosis：285、所有念珠菌属：3000 和非近平滑念珠菌属：5000）计算目标获得概率（PTA）。使用 EUCAST MIC 分布计算累积分数反应（CFR）。
第 1 天（83.31±15.87 与 71.31±14.24；P=0.008）和第 2 天（119.01±27.20 与 104.54±21.23；P=0.005）后滤器 AUC0-24（mg·h/L）值均高于预滤器值。MIC 为 0.125mg/L（切点=285）、0.016mg/L（切点=3000）和 0.008mg/L（切点=5000）时，第 1 天的 PTA≥90%，MIC 为 0.25mg/L（切点=285）和 0.016mg/L（切点=3000 和 5000）时，第 2 天的 PTA≥90%，且预滤器和后滤器值之间无差异。第 2 天，C. albicans（切点=3000 和 5000）和 C. glabrata（切点=3000）获得的 CFR＞90%，但 C. parapsilosis 除外。
CVVH 未去除米卡芬净，无需调整剂量，非近平滑念珠菌属具有最佳 PK/PD 覆盖，预滤器和后滤器 PD 等效。
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