Sato Masatoki, Ito Masaki, Suzuki Shigeo, Sakuma Hiroko, Takeyama Aya, Oda Shinichi, Watanabe Masahiro, Hashimoto Koichi, Miyazaki Kyohei, Kawasaki Yukihiko, Hosoya Mitsuaki
Department of Pediatrics, Fukushima Medical University, Fukushima, Japan
Department of Pediatrics, Soma General Hospital, Soma, Japan.
Antimicrob Agents Chemother. 2015 Mar;59(3):1643-9. doi: 10.1128/AAC.04263-14. Epub 2014 Dec 29.
We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage.
我们根据帕拉米韦在上呼吸道(URT)中的药代动力学,评估了当前单次使用帕拉米韦的疗效,并确定了预测性的帕拉米韦浓度-时间曲线,以评估其对神经氨酸酶抑制剂敏感性降低的病毒的疗效。从28例接受10mg/kg体重帕拉米韦治疗的患者中采集血清、鼻拭子或抽吸样本。使用定量实时逆转录PCR和神经氨酸酶抑制试验测量帕拉米韦给药后流感病毒RNA载量和敏感性的变化。测量了10mg/kg单次给药后血清和URT中的帕拉米韦浓度,并确定了预测性的血液和URT帕拉米韦浓度-时间曲线,以评估针对耐药变异体的各种给药方案。给药后24小时,帕拉米韦浓度降至血清中药物最大浓度(Cmax)的<0.1%。给药后48小时,帕拉米韦从URT中快速消除,这可能导致第3天后甲型流感病毒载量增加,但不会导致乙型流感病毒载量下降,尽管对帕拉米韦的敏感性没有降低。与每日一次给药相比,分次给药有望在URT中更长时间维持高水平的帕拉米韦。对于甲型和乙型流感病毒敏感性正常但无临床改善的患者,应考虑重新使用帕拉米韦。在由耐药变异体引起的严重病例中,与增加剂量的每日一次给药相比,分次给药有望获得更好的抑制效果和更少的不良事件。