title: In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in Japan.
abstract: The neuraminidase inhibitors oseltamivir phosphate (Tamiflu®), zanamivir (Relenza®), laninamivir octanoate (Inavir®), and peramivir (Rapiacta®) have been available for the treatment of influenza in Japan since 2010. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC₅₀) of each drug for influenza virus isolates from the 2011-2012 influenza season. Specimens were obtained from patients prior to treatment. Viral isolation was done using Madine-Darby canine kidney cells, and the type and subtype of influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate. The lineage of influenza B virus was determined by direct sequencing of the hemagglutinin gene. Influenza A(H3N2) and influenza B viruses were isolated in 283 and 42 patients, respectively, while no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC₅₀ value exceeding 50 nM for any of the neuraminidase inhibitors. IC50 values for A(H3N2) were similar between the 2010-2011 and 2011-2012 seasons. In contrast, the IC₅₀ values for influenza B viruses in the 2011-2012 season to the four drugs were significantly lower than those found in the 2010-2011 season. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC₅₀ values to increase in Japan at present.
authors.affiliation: Department of Clinical Trials, Center for Advanced Medical Innovation, Kyushu University, Japan; Japan Physicians Association, Tokyo, Japan. Electronic address: hikematsu@camiku.kyushu-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawai
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Iwaki
authors.affiliation: Japan Physicians Association, Tokyo, Japan.
authors.forename: Seizaburo
authors.initials: S
authors.lastname: Kashiwagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000302:isolation & purification; D009981:Influenza B virus / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D020128:Inhibitory Concentration 50; D007564:Japan / Q000453:epidemiology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase
keywords: 50% Inhibitory concentration; Influenza; Laninamivir; Oseltamivir; Peramivir; Zanamivir