PK/PD analysis of biapenem in patients undergoing continuous hemodiafiltration.
PK/PD analysis of biapenem in patients undergoing continuous hemodiafiltration.
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DOI：
10.1186/s40780-015-0031-6
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发表时间：
2015
影响因子：
1
通讯作者：
Sai Y
中科院分区：
文献类型：
--
作者：
Akashita G;Hosaka Y;Noda T;Isoda K;Shimada T;Sawamoto K;Miyamoto K;Taniguchi T;Sai Y
连续性血液透析滤过（CHDF）用作肾衰竭危重患者的肾脏替代治疗，并治疗高细胞因子血症。由于CHDF也清除治疗药物，药物药代动力学（PK）应取决于CHDF条件。尽管抗生素比阿培南（BIPM）用于CHDF患者，但此类患者的最佳治疗方案尚未完全阐明。在这项研究中，我们研究了BIPM在接受聚砜（PS）膜CHDF的不同肾功能水平患者中的PK，并使用PK模型确定最佳给药方案。接受CHDF的患者（n = 7）输注BIPM（300 mg）。采集血液和滤液-透析液进行隔室和非隔室分析。PS膜的筛分系数为1.00 ± 0.06（平均值±标准差，BIPM的CHDF清除率为透析液流速（QD）和滤液流速（QF）之和。非CHDF清除率显示个体间变异性（4.82 ± 2.48 L/h），取决于残余肾功能和非肾清除率。基于房室模型获得的平均PK参数，300 mg每6 h、300 mg每8 h和600 mg每12 h的方案达到最大杀灭终点（超过40% T > MIC 4 μg/mL）。MonteCarlo模拟结果表明，每6 h输注1 h，每次300 mg为最佳方案，达到MIC 2 μg/mL的概率为90.2%。我们的研究结果确定了不同肾功能水平的患者接受PS膜CHDF的最佳BIPM方案。
Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. Since CHDF also clears therapeutic agents, drug pharmacokinetics (PK) should be dependent upon CHDF conditions. Although the antibiotic biapenem (BIPM) is used in patients undergoing CHDF, the optimal therapeutic regimen in such patients has not been fully clarified. In this study, we investigated the PK of BIPM in patients with various levels of renal function undergoing CHDF with polysulfone (PS) membrane, and used PK models to identify the optimal administration regimen. BIPM (300 mg) was administered by infusion in patients undergoing CHDF (n = 7). Blood and filtrate-dialysate were collected for compartment and non-compartment analysis. The sieving coefficient of PS membrane was 1.00 ± 0.06 (mean ± S.D., n = 7), and CHDF clearance of BIPM was found to be the sum of the dialysate flow rate (QD) and filtrate flow rate (QF). Non-CHDF clearance showed inter-individual variability (4.82 ± 2.48 L/h), depending on residual renal function and non-renal clearance. Based on the average PK parameters obtained with a compartmental model, maximal kill end point (over 40 % T > MIC4 μg/mL) was achieved with regimens of 300 mg every 6 h, 300 mg every 8 h, and 600 mg every 12 h. Monte Carlo simulation indicated that 300 mg infusion for 1 h every 6 h was optimal, and the probability of target attainment at MIC2 μg/mL was 90.2 %. Our results establish the optimal regimen of BIPM in patients with various levels of renal function undergoing CHDF with a PS membrane.