Peramivir Pharmacokinetics in Two Critically Ill Adults with 2009 H1N1 Influenza A Concurrently Receiving Continuous Renal Replacement Therapy
Peramivir Pharmacokinetics in Two Critically Ill Adults with 2009 H1N1 Influenza A Concurrently Receiving Continuous Renal Replacement Therapy
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DOI：
10.1592/phco.30.10.1016
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发表时间：
2010-10-01
期刊：
影响因子：
4.1
通讯作者：
Goff, Debra A.
中科院分区：
文献类型：
--
作者：
Bazan, Jose A.;Bauer, Karri A.;Goff, Debra A.
研究目的。在同时接受连续性肾脏替代治疗（CRRT）的患者中，确定静脉注射帕拉米韦（一种研究性神经氨酸酶抑制剂，用于治疗2009年H1N1感染或被认为是2009年H1N1病毒的非亚型甲型流感）的药代动力学。药代动力学分析。设置。一所大学附属医院的重症监护室。两名患有2009年H1N1甲型流感的危重女性患者接受了同情使用的静脉内帕拉米韦治疗，每日输注600 mg，持续30分钟，同时接受连续静脉-静脉血液透析滤过（CVVHDF），一种CRRT形式。测量和主要结果。在第四次（第一名患者）和第九次（第二名患者）帕拉米韦输注前和输注后30分钟从两名患者采集血浆样品，以分别估计最小（C-min）和最大（C-max）血浆浓度。在接受CVVHDF时，测量每例患者的两个额外的输注后浓度，以估计帕拉米韦的非房室药代动力学参数。两例患者的C-min分别为2170和251 ng/ml，C-max分别为18,400和20,300 ng/ml，0-24小时血药浓度-时间曲线下面积AUC（0-24）分别为178，000和94，400 ng. h/ml，药物清除率分别为56和106 ml/min，血浆半衰期分别为7.6和3.7小时。在稳态时，根据理想体重调整的分布容积分别为0.51和0.54 L/kg。第1例患者的帕拉米韦血浆清除率低于第2例患者，但根据AUC（0-24）计算的2例患者的帕拉米韦清除率均高于CRRT预测值。因此，这些患者静脉注射帕拉米韦的剂量是合适的。需要额外的药代动力学数据来证实这些结果，并帮助指导接受各种形式CRRT的患者的给药。
Study Objective. To determine the pharmacokinetics of intravenous peramivir-an investigational neuraminidase inhibitor for the treatment of 2009 H1N1 infection or nonsubtypable influenza A thought to be the 2009 H1N1 virus in patients concurrently receiving continuous renal replacement therapy (CRRT).Design. Pharmacokinetic analysis.Setting. Critical care unit at a university-affiliated hospital.Patients. Two critically ill women with 2009 H1N1 influenza A treated with compassionate-use intravenous peramivir administered as a daily infusion of 600 mg over 30 minutes while receiving continuous venovenous hemodiafiltration (CVVHDF), a form of CRRT.Measurements and Main Results. Plasma samples were collected from the two patients before and 30 minutes after the fourth (first patient) and ninth (second patient) peramivir infusion to estimate minimum (C-min) and maximum (C-max) plasma concentrations, respectively. Two additional postinfusion concentrations were measured from each patient to estimate noncompartmental pharmacokinetic parameters of peramivir while receiving CVVHDF. In the two patients, respectively, C-min was 2170 and 251 ng/ml, C-max was 18,400 and 20,300 ng/ml, area under the plasma concentration time curve from 0-24 hours (AUC(0-24)) was 178,000 and 94,400 ng.hour/ml, drug clearance was 56 and 106 ml/minutes, and plasma half-life was 7.6 and 3.7 hours. The volume of distribution adjusted for ideal body weight at steady state was 0.51 and 0.54 L/kg, respectively.Conclusion. The first patient had a slower peramivir plasma clearance compared with the second patient, but both patients had higher peramivir clearances as calculated from AUC(0-24) than those predicted by CRRT. Thus, the dosage of intravenous peramivir was appropriate in these patients. Additional pharmacokinetic data are needed to confirm these results and help guide dosing in patients receiving various forms of CRRT.