Saisho Yutaka, Ishibashi Toru, Fukuyama Hidenori, Fukase Hiroyuki, Shimada Jingoro
Medical Affairs Department, Shionogi & Co., Ltd, Osaka, Japan.
Clinical Research Department, Shionogi & Co., Ltd, Osaka, Japan.
Antivir Ther. 2017;22(4):313-323. doi: 10.3851/IMP3104. Epub 2016 Nov 2.
Intravenous peramivir is a potent neuraminidase (NA) inhibitor with activity against influenza A and B viruses. The early use of NA inhibitors has been shown to reduce mortality in influenza patients.
To evaluate the pharmacokinetics of peramivir and confirm the safety and tolerability of multiple infusions of peramivir in healthy Japanese subjects, two Phase I, single-centre, randomized, double-blind and placebo-controlled studies consisting of a multiple-dose study and a high-dose study were conducted.
Multiple intravenous infusions of peramivir were well tolerated up to 800 mg once a day and 400 mg twice daily for 6 days. Dose proportionalities for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were established up to the 800 mg dose. Approximately 90% of unchanged peramivir was excreted into urine within 12 h after treatment with 800 mg of peramivir. The peramivir plasma and upper respiratory tract fluid levels were significantly higher than the 50% inhibition concentrations for NA enzyme activity (IC) of epidemic influenza viruses, including those harbouring the H274Y mutation.
The pharmacokinetic properties obtained here for intravenous peramivir are consistent with the previously reported clinical efficacy and safety of this antiviral.
静脉注射帕拉米韦是一种强效神经氨酸酶（NA）抑制剂，对甲型和乙型流感病毒均有活性。已证明早期使用NA抑制剂可降低流感患者的死亡率。
为了评估帕拉米韦的药代动力学，并确认多次输注帕拉米韦在健康日本受试者中的安全性和耐受性，开展了两项I期单中心随机双盲安慰剂对照研究，包括一项多剂量研究和一项高剂量研究。
帕拉米韦每日一次800 mg及每日两次400 mg，连续6天的多次静脉输注耐受性良好。在800 mg剂量范围内建立了最大血浆浓度（Cmax）和血浆浓度-时间曲线下面积（AUC）的剂量比例关系。用800 mg帕拉米韦治疗后，约90%未改变的帕拉米韦在12小时内排泄到尿液中。帕拉米韦的血浆和上呼吸道液体水平显著高于包括携带H274Y突变的流行流感病毒的NA酶活性50%抑制浓度（IC）。
此处获得的静脉注射帕拉米韦的药代动力学特性与该抗病毒药物先前报道的临床疗效和安全性一致。
