Biological Research Laboratories, Daiichi Sankyo Co. Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, Japan.
J Infect Chemother. 2012 Feb;18(1):69-74. doi: 10.1007/s10156-011-0292-4. Epub 2011 Sep 1.
Laninamivir octanoate (Inavir(®); Daiichi Sankyo, Tokyo, Japan) is an anti-influenza drug that provides complete treatment by a single inhalation. It works as a long-acting neuraminidase (NA) inhibitor by means of high and continuous exposure of laninamivir, its active metabolite, in the lungs of mice after intranasal administration. Even after 6 days after intranasal administration of 236 μg/kg laninamivir octanoate, the concentration of laninamivir in the lungs was maintained more than 2-3 orders higher than 50% inhibitory concentrations of laninamivir to N1 NAs, about 2 orders higher than N2 NA of seasonal influenza A viruses, and more than about 50 times higher than influenza B virus NA. From A/H1N1 influenza virus-infected and laninamivir octanoate-treated mice, no low-susceptibility mutants to laninamivir were obtained. In contrast, four different mutants to oseltamivir were obtained from mice administered oseltamivir phosphate, which required repeated administration for treatment under the experimental condition, showing similar virus load reduction between both compounds. This finding suggested the unique characteristics of laninamivir octanoate in mice may work suppressively to generate low-susceptibility mutants.
八氮杂双环壬烷羧酸莱那司他（Inavir®；第一三共株式会社，日本东京）是一种抗流感药物，通过单次吸入即可完成治疗。它通过鼻腔给予后在小鼠肺部中高浓度和持续暴露其活性代谢物 laninamivir，起到长效神经氨酸酶（NA）抑制剂的作用。即使在经鼻腔给予 236μg/kg 八氮杂双环壬烷羧酸莱那司他 6 天后，肺部中的 laninamivir 浓度仍维持在高于对 N1 NAs 的 50%抑制浓度 2-3 个数量级以上，高于季节性流感 A 病毒的 N2 NA 约 2 个数量级，高于流感 B 病毒 NA 约 50 倍以上。从感染 A/H1N1 流感病毒并经八氮杂双环壬烷羧酸莱那司他治疗的小鼠中，未获得对 laninamivir 低敏感性的突变体。相比之下，从经磷酸奥司他韦治疗的小鼠中获得了对 oseltamivir 的四个不同突变体，而在实验条件下，需要重复给予 oseltamivir phosphate 进行治疗，这两种化合物的病毒载量降低程度相似。这一发现表明，八氮杂双环壬烷羧酸莱那司他在小鼠中的独特特征可能具有抑制作用，从而产生低敏感性突变体。
