title: Efficacy of a single intravenous administration of laninamivir (an active metabolite of laninamivir octanoate) in an influenza virus infection mouse model.
abstract: Laninamivir, a potent neuraminidase (NA) inhibitor, is an active metabolite of laninamivir octanoate (code name: CS-8958) which is a long acting NA inhibitor and is commercially available under the brand name Inavir in Japan to complete the treatment of influenza by a single inhalation. It is supposed that the long acting character is provided by the long retention of laninamivir in the respiratory tract after intranasal administration of laninamivir octanoate in mice and with stable binding of laninamivir to NA of various influenza viruses such as N1, N2 subtypes and NA of B virus. Peramivir, another NA inhibitor, is also approved in Japan as a single intravenous infusion. In spite of the quick disappearance of peramivir from the blood after injection, the reason treatment can be completed by a single administration is thought to be that peramivir showed stable binding to NA with N9 subtype. Therefore, the stable binder, laninamivir is possibly effective by a single intravenous administration in the mouse model infected with influenza viruses. A single intravenous administration of laninamivir and peramivir at 30mg/kg significantly prolonged mice survival at a comparable level in the mouse lethal model infected with the A/PR/8/34 (H1N1) virus. Also, a single intravenous administration of laninamivir and peramivir significantly suppressed virus proliferation in the lungs of mice infected with influenza B virus. Thus, laninamivir may be effective by a single intravenous infusion in treating influenza, the same as peramivir.
authors: Biological Res. Labs., Daiichi Sankyo Co. Ltd., Japan.
authors: Masayo
authors: M
authors: Kakuta
authors: Shuku
authors: S
authors: Kubo
authors: Mikiko
authors: M
authors: Tanaka
authors: Satoko
authors: S
authors: Tobiume
authors: Takanori
authors: T
authors: Tomozawa
authors: Makoto
authors: M
authors: Yamashita
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006146:Guanidines; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011714:Pyrans; D012794:Sialic Acids; D053243:Zanamivir / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; C546918:laninamivir; D053243:Zanamivir
keywords: 50% mouse lethal dose; AUC; BSA; FBS; Influenza; Intravenous administration; Laninamivir; MDCK; MLD(50); MRT; Madin–Darby canine kidney; Mouse model; Neuraminidase inhibitor; PBS; area under curve; bovine serum albumin; days postinfection; dpi; fetal bovine serum; half-life; hours postinfection; hpi; mean residence time; pfu; phosphate buffered saline; plaque forming unit; t(1/2)