Bentley Michael L, Hollistera Alan S, Hansenb Amanda C, Smith Jean A, Cain James S
Int J Clin Pharmacol Ther. 2014 Dec;52(12):1105-11. doi: 10.5414/CP202161.
Peramivir is a neuraminidase inhibitor having activity against various influenza A and B subtypes. The main route of elimination is the kidney and a dose reduction is justified for multiple-day therapy when the creatinine clearance is < 50 mL/min. Before the 2009 influenza pandemic, dosing guidelines did not exist for patients receiving continuous renal replacement therapy (CRRT). This case report provides data on the dialysis membrane saturation coefficient (SA) and pharmacokinetic parameters of peramivir in a 29-year-old female receiving continuous veno-venous hemodiafiltration (CVVHDF), a mode of CRRT.
Plasma and effluent samples were collected to calculate the saturation coefficient, plasma half-life, maximum and minimum plasma concentrations, and area under the plasma drug concentration-time curve (AUC) for peramivir. CVVHDF was performed using a Prisma pump and an AN69 filter. During peramivir sampling, the dialysate flow rate was 16.7 mL/min. The mean total ultrafiltrate produced was 14.2 mL/min. To calculate a saturation coefficient (SA), simultaneous sampling of blood and effluent was performed. Pre- and post-filter as well as effluent samples were obtained 4.5 and 8.5 hours following the 3rd dose of 480 mg. Plasma concentrations were also obtained at several time points and the AUC estimated from 0 to 24 hours (AUC0-24).
The maximum plasma concentration (C30min) was 19,477 ng/mL, the minimum plasma concentration (Cmin) 2,750 ng/mL, and AUC0-24 196,166 ng x h/mL. The estimated plasma half-life was 8.2 hours with a log-linear decrease over the 24-hour period suggesting significant extracorporeal clearance. The calculated SA was 0.98, similar to an estimated SA of 1.
Peramivir is readily cleared by CVVHDF having a calculated SA close to 1. The maximum and minimum plasma concentrations, AUC0-24, and plasma half-life was similar to those previously reported. These data will be useful in determining appropriate peramivir dosing regimens for severely ill influenza patients with acute renal impairment managed by CVVHDF.
帕拉米韦是一种对多种甲型和乙型流感亚型均有活性的神经氨酸酶抑制剂。其主要消除途径是肾脏，当肌酐清除率<50 mL/分钟时，多日治疗时减少剂量是合理的。在2009年流感大流行之前，对于接受持续肾脏替代治疗（CRRT）的患者不存在给药指南。本病例报告提供了一名接受持续静脉-静脉血液透析滤过（CVVHDF，一种CRRT模式）的29岁女性患者中帕拉米韦的透析膜饱和系数（SA）和药代动力学参数的数据。
收集血浆和流出液样本以计算帕拉米韦的饱和系数、血浆半衰期、血浆最大和最小浓度以及血浆药物浓度-时间曲线下面积（AUC）。使用Prisma泵和AN69滤器进行CVVHDF。在帕拉米韦采样期间，透析液流速为16.7 mL/分钟。平均总超滤量为14.2 mL/分钟。为计算饱和系数（SA），同时采集血液和流出液样本。在第3剂480 mg给药后4.5小时和8.5小时获得滤器前、滤器后以及流出液样本。还在多个时间点获得血浆浓度并估计0至24小时的AUC（AUC0-24）。
血浆最大浓度（C30min）为19,477 ng/mL，血浆最小浓度（Cmin）为2,750 ng/mL，AUC0-24为196,166 ng·h/mL。估计的血浆半衰期为8.2小时，在24小时内呈对数线性下降，提示有显著的体外清除。计算出的SA为0.98，与估计的SA 1相似。
帕拉米韦很容易被CVVHDF清除，计算出的SA接近1。血浆最大和最小浓度、AUC0-24以及血浆半衰期与先前报道的相似。这些数据将有助于确定通过CVVHDF治疗的急性肾损伤重症流感患者的合适帕拉米韦给药方案。
