Laninamivir

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Seizaburo Kashiwagi - One of the best experts on this subject based on the ideXlab platform.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016 17 japanese influenza season comparison with the 2011 12 to 2015 16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate comparison of the 2011 12 to 2015 16 japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate; comparison of the 2011/12 to 2015/16 Japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate for influenza treatment comparison among the four japanese influenza seasons from 2011 2012 to 2014 2015
    Journal of Infection and Chemotherapy, 2016
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and other symptoms as markers of the clinical effectiveness of Laninamivir octanoate hydrate (Laninamivir) were investigated in the Japanese 2014–2015 influenza season and the results were compared with those of the previous three seasons, 2011–2012 to 2013–2014. From these four seasons, the data of 636 influenza A(H3N2) and 128 influenza B patients was available for analysis. No significant difference was found in their baseline characteristics. The median duration of fever for all A(H3N2) patients ranged from 32.0 to 41.0 h. The duration of fever in the 2014–2015 season was significantly shorter than that in the 2012–2013 and 2013–2014 seasons (p = 0.0204 and 0.0391, respectively), but the differences were within nine hours. The median duration of symptoms for A(H3N2) ranged from 80.0 to 89.0 h, with no significant difference among the four seasons (p = 0.2222). The median duration of fever for B patients ranged from 43.0 to 50.0 h, with no significant difference among the four seasons. The duration of the symptoms for B varied by season, but no significant difference was found among the four seasons. Over the four seasons, 44 adverse events were reported from among 921 patients, with all resolving without treatment. These results indicate the continuing effectiveness of Laninamivir against influenza A(H3N2) and B, with no safety issues. It is unlikely that the clinical use of Laninamivir has caused viral resistance in the currently epidemic viruses.

Hideyuki Ikematsu - One of the best experts on this subject based on the ideXlab platform.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016 17 japanese influenza season comparison with the 2011 12 to 2015 16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate comparison of the 2011 12 to 2015 16 japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate; comparison of the 2011/12 to 2015/16 Japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate for influenza treatment comparison among the four japanese influenza seasons from 2011 2012 to 2014 2015
    Journal of Infection and Chemotherapy, 2016
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and other symptoms as markers of the clinical effectiveness of Laninamivir octanoate hydrate (Laninamivir) were investigated in the Japanese 2014–2015 influenza season and the results were compared with those of the previous three seasons, 2011–2012 to 2013–2014. From these four seasons, the data of 636 influenza A(H3N2) and 128 influenza B patients was available for analysis. No significant difference was found in their baseline characteristics. The median duration of fever for all A(H3N2) patients ranged from 32.0 to 41.0 h. The duration of fever in the 2014–2015 season was significantly shorter than that in the 2012–2013 and 2013–2014 seasons (p = 0.0204 and 0.0391, respectively), but the differences were within nine hours. The median duration of symptoms for A(H3N2) ranged from 80.0 to 89.0 h, with no significant difference among the four seasons (p = 0.2222). The median duration of fever for B patients ranged from 43.0 to 50.0 h, with no significant difference among the four seasons. The duration of the symptoms for B varied by season, but no significant difference was found among the four seasons. Over the four seasons, 44 adverse events were reported from among 921 patients, with all resolving without treatment. These results indicate the continuing effectiveness of Laninamivir against influenza A(H3N2) and B, with no safety issues. It is unlikely that the clinical use of Laninamivir has caused viral resistance in the currently epidemic viruses.

Hitoshi Ishizuka - One of the best experts on this subject based on the ideXlab platform.

  • intrapulmonary pharmacokinetics of Laninamivir in healthy subjects comparison between a nebulizer and a dry powder inhaler
    European Respiratory Journal, 2018
    Co-Authors: Hitoshi Ishizuka, Hidetoshi Furuie, Kaoru Toyama
    Abstract:

    Background: Laninamivir octanoate (LO), an octanoyl prodrug of Laninamivir, is a long-acting neuraminidase inhibitor exhibiting efficacy to treat adult patients with influenza virus infection by a single inhalation using a nebulizer (NEB) or a dry powder inhaler (DPI). Objectives: Intrapulmonary pharmacokinetics (PK) of LO and Laninamivir after a single inhalation using NEB were evaluated by bronchoalveolar lavage (BAL) in healthy subjects and compared with those using DPI to consider an appropriate LO dose for NEB. Methods: BAL was performed at specified time intervals following a single LO inhalation (160 mg) as a suspension using NEB in healthy Japanese male adults. LO and Laninamivir concentrations in BAL fluid were analyzed by validated LC-MS/MS methods. The concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. PK parameters were determined using a non-compartment analysis and compared with those obtained from the previous BAL study using DPI (LO dose was 40 mg). Results: ELF concentrations of LO and Laninamivir after the inhalation using NEB were relatively higher than those using DPI in each evaluated time point. LO and Laninamivir AUC after the inhalation using NEB was higher than for DPI. T1/2 of LO and Laninamivir did not change between NEB and DPI. Laninamivir concentrations in ELF notably exceeded the IC50 values for viral neuraminidase at all time points examined both using NEB and DPI. Conclusion: ELF concentration profiles of Laninamivir support its long-lasting effect to treat patients with influenza virus infection by a single administration of 160 mg of LO using NEB.

  • Intrapulmonary Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, after a Single Nebulized Administration of Laninamivir Octanoate in Healthy Japanese Subjects
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Kaoru Toyama, Hidetoshi Furuie, Hitoshi Ishizuka
    Abstract:

    A single dose of Laninamivir octanoate (LO) inhaled using a dry powder inhaler (DPI) is effective for the treatment and prophylaxis of influenza. Nebulizers are an option for pediatric and elderly patients who may have difficulty in using a DPI. A single-center, open-label study was conducted to evaluate the plasma and intrapulmonary pharmacokinetics (PK) of Laninamivir after a single nebulized administration of LO in healthy male Japanese subjects for identifying a safe and effective dosage regimen for a nebulizer. A single dose of LO (40 to 320 mg) was administered using a nebulizer, and plasma concentrations of LO and Laninamivir were analyzed up to 168 h after inhalation by validated liquid chromatography-tandem mass spectrometry methods. Subgroups of 6 subjects each underwent bronchoalveolar lavage at specified time intervals over 4 to 168 h following a single nebulized administration of LO (160 mg), and the concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. PK parameters were determined by noncompartment analysis. Inhaled nebulized LO was found to be safe and well tolerated up to the highest dose evaluated (320 mg). Plasma Laninamivir concentrations increased almost dose proportionally. Laninamivir concentrations in ELF exceeded the 50% inhibitory concentrations for viral neuraminidase up to 168 h after the nebulized inhalation of 160 mg LO. Thus, similarly to the DPI, ELF concentration profiles of Laninamivir after a single nebulized administration support its long-lasting effect against influenza virus infection. This study has been registered at JAPIC Clinical Trials Information (http://www.clinicaltrials.jp/) under registration no. JAPIC CTI-152996.

  • Laninamivir s prolonged intrapulmonary retention intrapulmonary pharmacokinetics pk and the intracellular disposition to support the long lasting efficacy after an inhaled administration of its prodrug Laninamivir octanoate lo
    European Respiratory Journal, 2013
    Co-Authors: Hidetoshi Furuie, Daisuke Nakai, Kumiko Koyama, Kaoru Toyama, Hitoshi Ishizuka
    Abstract:

    Background: A single inhaled dose of LO, a long-acting neuraminidase inhibitor, exhibits efficacy to patients with influenza virus infection. However, the relation between PK and its long-lasting efficacy has not fully been investigated. Purpose: Intrapulmonary PK in healthy volunteers and the intracellular drug disposition in mice were evaluated to support its long-lasting efficacy. Methods: Each subject underwent bronchoalveolar lavage (BAL) at specified time intervals from 4 to 240 hrs after an inhaled LO dosing (40mg). Plasma, BAL fluid and alveolar macrophage (AM) were analyzed to determine drug concentrations. Microautoradiographic localization in the respiratory tissues in mice and the drug uptake and release were evaluated using primary cultured airway epithelial cells. Results: In healthy volunteers, Laninamivir concentration in epithelial lining fluid (ELF) and AM were higher than those in plasma and lasted for 240 hrs. Laninamivir in ELF decreased with a longer half-life (∼ 6 days) and notably exceeded the IC50 values for viral neuraminidase at all time points. In mice, the labeled LO mainly located on the epithelial cells for a long period. LO uptake in epithelial cells increased without saturation and the intracellular Laninamivir was released very slowly, which was regarded as a rate-limiting step in the cellular retention. Conclusion: ELF concentration profiles and prolonged high intrapulmonary retention of Laninamivir support its long lasting efficacy to treat patients with influenza virus infection by the single inhalation.

  • population pharmacokinetics of Laninamivir and its prodrug Laninamivir octanoate in healthy subjects and in adult and pediatric patients with influenza virus infection
    Drug Metabolism and Pharmacokinetics, 2013
    Co-Authors: Kazutaka Yoshihara, Hitoshi Ishizuka, Yuichi Kubo
    Abstract:

    Summary: Laninamivir octanoate (LO) is a new neuraminidase inhibitor for inhalation. The objectives of this study were to model the population pharmacokinetics of LO and its active metabolite Laninamivir after inhaled administration of LO using a pooled population of healthy subjects, and adult and pediatric patients with influenza virus infection from 8 clinical studies, and to evaluate covariate effects on pharmacokinetics. The pharmacokinetics of LO and Laninamivir in plasma and urine are well-described by structural models that consist of a 2-compartment model for LO with instantaneous bolus input and first-order elimination; and a 1-compartment model for Laninamivir with formation of Laninamivir via the metabolic pathway from LO in systemic circulation, entry of Laninamivir from the respiratory tract compartment, and linear elimination. Creatinine clearance was identified as a covariate of apparent total clearance for LO and renal clearances for LO and Laninamivir, with the largest effect on Laninamivir exposure. Body weight was identified to affect distribution volumes of LO and Laninamivir and the metabolic clearance of LO; however there was no notable effect on exposures across the wide body weight range evaluated. The population pharmacokinetic model also provides insight into the likely kinetics of drug disposition in the respiratory tract following inhaled administration.

  • intrapulmonary distribution and pharmacokinetics of Laninamivir a neuraminidase inhibitor after a single inhaled administration of its prodrug Laninamivir octanoate in healthy volunteers
    Antimicrobial Agents and Chemotherapy, 2012
    Co-Authors: Hitoshi Ishizuka, Satoshi Yoshiba, Hiromi Okabe, Kaoru Toyama, Hidetoshi Furuie
    Abstract:

    A single inhaled dose of Laninamivir octanoate (LO), a long-acting neuraminidase inhibitor, exhibits efficacy in treating both adult and pediatric patients with influenza virus infection. The intrapulmonary pharmacokinetics (PK) of LO and Laninamivir, a pharmacologically active metabolite, were investigated by a single-center, open-label study of healthy adult volunteers. Subgroups of five subjects each underwent bronchoalveolar lavage (BAL) 4, 8, 24, 48, 72, 168, and 240 h following a single inhaled administration of LO (40 mg). Plasma, BAL fluid, and alveolar macrophages (AM) were analyzed to determine LO and Laninamivir concentrations, using validated liquid chromatography-tandem mass spectrometry methods. The concentrations in epithelial lining fluid (ELF) and AM from the first and subsequent BAL fluid samples were determined separately to explore the drug distribution in airways. Mean Laninamivir concentrations in ELF, calculated using the first BAL fluids and BAL fluids collected 4 h after inhaled administration, were 8.57 and 2.40 μg/ml, respectively. The Laninamivir concentration in ELF decreased with a longer half-life than that in plasma, and it exceeded the 50% inhibitory concentrations for viral neuraminidases at all time points examined for 240 h after the inhalation. Laninamivir exposure in ELF from the first BAL samples was 3.2 times higher than that in ELF from the subsequent BAL fluid samples. ELF concentration profiles of Laninamivir support its long-lasting effect for treatment of patients with influenza virus infection by a single inhaled administration.

Naoki Kawai - One of the best experts on this subject based on the ideXlab platform.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016 17 japanese influenza season comparison with the 2011 12 to 2015 16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate in the 2016/17 Japanese influenza season; comparison with the 2011/12 to 2015/16 seasons
    Journal of Infection and Chemotherapy, 2018
    Co-Authors: Hideyuki Ikematsu, Seizaburo Kashiwagi, Hiroki Yamaguchi, Naoki Kawai, Norio Iwaki, Yusuke Ishikawa, Kazuhito Shiosakai
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2016/17 influenza season and the results were compared with those of the 2011/12 to 2015/16 seasons. A total of 1278 patients were evaluated for the duration of fever and symptoms in the six studied seasons. In the 2016/17 season, the influenza types/subtypes of the patients were 6 A (H1N1)pdm09 (2.9%), 183 A (H3N2) (87.6%), and 20 B (9.6%). The respective median durations of fever for A (H1N1)pdm09, A (H3N2), and B were 38.0, 33.0, and 38.5 h, without significant difference (p = 0.9201), and the median durations of symptoms were 86.5, 73.0, and 99.0 h, with significant difference (p = 0.0342). The median durations of fever and symptoms after Laninamivir inhalation were quite consistent for the six studied seasons for A (H1N1)pdm09, A (H3N2), and B, without any significant differences. The percentage of patients with unresolved fever patients displayed a similar pattern through the six studied seasons for all these virus types. There was no significant difference in the duration of fever or symptoms between the Victoria and Yamagata lineages in the 2016/17 season and those of the previous studied seasons. Over the seasons tested, ten adverse drug reactions (ADRs) were reported from 1341 patients. The most frequent ADR was diarrhea and all ADRs were self-resolving and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A (H1N1)pdm09, A (H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate comparison of the 2011 12 to 2015 16 japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • Duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate; comparison of the 2011/12 to 2015/16 Japanese influenza seasons
    Journal of Infection and Chemotherapy, 2017
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and symptoms after Laninamivir octanoate hydrate (Laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47.0 h, and the median durations of symptoms were 87.0, 76.0, and 93.0 h for A(H1N1)pdm09, A(H3N2), and B, respectively, with no significant difference. The median durations of fever were 52.0 and 46.0 h and the median durations of symptoms 93.0 and 88.0 h for the Victoria and Yamagata B lineages, respectively, with no significant difference. Fever resolution after Laninamivir inhalation by the A(H1N1)pdm09 patients was similar in the 2013/14 and 2015/16 seasons. Fever resolution after Laninamivir inhalation was similar in all comparisons of the 2011/12 to 2015/16 seasons for both A(H3N2) and B, with no significant difference among the five seasons. Over the seasons tested, eight adverse drug reactions (ADRs) were reported for 1128 patients. The most frequent ADR was diarrhea, and all ADRs were resolved and not serious. These results indicate the continuing clinical effectiveness of Laninamivir against influenza A(H1N1)pdm09, A(H3N2), and B, with no safety issues.

  • duration of fever and other symptoms after the inhalation of Laninamivir octanoate hydrate for influenza treatment comparison among the four japanese influenza seasons from 2011 2012 to 2014 2015
    Journal of Infection and Chemotherapy, 2016
    Co-Authors: Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
    Abstract:

    Abstract The duration of fever and other symptoms as markers of the clinical effectiveness of Laninamivir octanoate hydrate (Laninamivir) were investigated in the Japanese 2014–2015 influenza season and the results were compared with those of the previous three seasons, 2011–2012 to 2013–2014. From these four seasons, the data of 636 influenza A(H3N2) and 128 influenza B patients was available for analysis. No significant difference was found in their baseline characteristics. The median duration of fever for all A(H3N2) patients ranged from 32.0 to 41.0 h. The duration of fever in the 2014–2015 season was significantly shorter than that in the 2012–2013 and 2013–2014 seasons (p = 0.0204 and 0.0391, respectively), but the differences were within nine hours. The median duration of symptoms for A(H3N2) ranged from 80.0 to 89.0 h, with no significant difference among the four seasons (p = 0.2222). The median duration of fever for B patients ranged from 43.0 to 50.0 h, with no significant difference among the four seasons. The duration of the symptoms for B varied by season, but no significant difference was found among the four seasons. Over the four seasons, 44 adverse events were reported from among 921 patients, with all resolving without treatment. These results indicate the continuing effectiveness of Laninamivir against influenza A(H3N2) and B, with no safety issues. It is unlikely that the clinical use of Laninamivir has caused viral resistance in the currently epidemic viruses.

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  • long acting neuraminidase inhibitor Laninamivir octanoate as post exposure prophylaxis for influenza
    Clinical Infectious Diseases, 2016
    Co-Authors: Seizaburo Kashiwagi, Akira Watanabe, Mitsutoshi Uemori, Hideyuki Ikematsu, Shinichiro Awamura
    Abstract:

    Close contact with an influenza patient increases the risk of subsequent infection. In such cases, antiviral chemoprophylaxis should be considered for persons at high risk from serious illness or death related to influenza (the elderly, those with chronic respiratory illness or metabolic disorders including diabetes mellitus, chronic heart disease, and immunodeficiency) [1, 2]. A single administration of Laninamivir octanoate, a long-acting neuraminidase inhibitor, has been demonstrated to be an effective treatment for influenza [3–5], while oseltamivir and zanamivir need repeated administration, twice daily for 5 days. In Japan, Laninamivir octanoate has been used widely not only because of its high level of efficacy and safety but also because of its convenience [6–8]. For the post-exposure prophylaxis of influenza, the inhalation of 20 mg of Laninamivir octanoate once daily for 2 or 3 days effectively prevented the development of influenza through household contacts in a study conducted during the 2011–2012 influenza season [9]. However, it was not demonstrated that a single inhalation of Laninamivir octanoate was effective for post-exposure prophylaxis. In a study conducted during the 2009 influenza pandemic season, the inhalation of 20 or 40 mg of Laninamivir octanoate once a week reduced the proportion of patients who developed influenza (relative risk reduction [RRR] compared with placebo, 45.8% and 43.2%, respectively), but the differences with placebo were not significant [10]. A pharmacokinetics finding that a relatively high Laninamivir concentration persisted in the lungs for 10 days after a single inhalation [11] suggested that a single inhalation of Laninamivir octanoate may be effective for post-exposure prophylaxis. This study was conducted to evaluate the efficacy of a single inhalation of 40 mg of Laninamivir octanoate as post-exposure prophylaxis for household contacts.

  • Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial
    Journal of Infection and Chemotherapy, 2013
    Co-Authors: Seizaburo Kashiwagi, Akira Watanabe, Mitsutoshi Uemori, Hideyuki Ikematsu, Shinichiro Awamura, Takako Okamoto, Katsuyasu Ishida
    Abstract:

    Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether Laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of Laninamivir octanoate once daily for 2 days (LO-2), 20 mg of Laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group ( P  

  • A randomized double-blind controlled study of Laninamivir compared with oseltamivir for the treatment of influenza in patients with chronic respiratory diseases
    Journal of Infection and Chemotherapy, 2013
    Co-Authors: Akira Watanabe
    Abstract:

    Influenza infection tends to be severe in patients with chronic underlying diseases. This study evaluated the efficacy and safety of Laninamivir octanoate, an inhaled neuraminidase inhibitor, for the treatment of influenza patients with chronic respiratory diseases; we conducted a double-blind, randomized controlled trial to compare the efficacy and safety of Laninamivir octanoate and oseltamivir for the treatment of influenza in these patients. A total of 203 patients aged ≥20 years were randomized to receive either Laninamivir octanoate or oseltamivir. The primary efficacy endpoint was the time to illness alleviation. This study is registered with JapicCTI; the registration number is JapicCTI-090940. The full analysis set (FAS) included a total of 201 patients (Laninamivir group, n  = 101; oseltamivir group, n  = 100). Most patients had underlying bronchial asthma and 170 patients were infected with influenza A(H1N1)2009. The median time to illness alleviation was 64.7 h in the Laninamivir group and 59.7 h in the oseltamivir group, with a difference of 5.0 h between the two groups (95 % confidence interval, −13.6 to 16.1 h). No adverse events specific to Laninamivir octanoate were observed, and adverse events such as bronchospasm, which has been reported to be observed with other inhaled drugs related to Laninamivir octanoate, did not occur. Laninamivir octanoate showed similar efficacy and safety to oseltamivir in the treatment of influenza, including that caused by influenza A(H1N1)2009, in patients with chronic respiratory diseases.

  • Laninamivir octanoate for post exposure prophylaxis of influenza in household contacts a randomized double blind placebo controlled trial
    Journal of Infection and Chemotherapy, 2013
    Co-Authors: Seizaburo Kashiwagi, Akira Watanabe, Mitsutoshi Uemori, Hideyuki Ikematsu, Shinichiro Awamura, Takako Okamoto, Katsuyasu Ishida
    Abstract:

    Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether Laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of Laninamivir octanoate once daily for 2 days (LO-2), 20 mg of Laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P < 0.001 for each of the Laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7–85.8] and 78.1 % (95 % CI 64.1–86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the Laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20 mg of Laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts.

  • long acting neuraminidase inhibitor Laninamivir octanoate versus oseltamivir for treatment of influenza a double blind randomized noninferiority clinical trial
    Clinical Infectious Diseases, 2010
    Co-Authors: Akira Watanabe, Shanchwen Chang, Yasuo Ohashi
    Abstract:

    Background. A single administration of Laninamivir octanoate, a long-acting neuraminidase inhibitor, against influenza infection has been proven effective in nonclinical studies. This study evaluated the clinical efficacy of Laninamivir octanoate for the treatment of adult influenza patients. Methods. A double-blind, randomized controlled trial examined whether Laninamivir octanoate was noninferior to oseltamivir. A total of 1003 patients aged ≥20 years with febrile influenza symptoms for no more than 36 h were randomized to receive either 40 mg of Laninamivir octanoate, 20 mg of Laninamivir octanoate, or oseltamivir. Laninamivir octanoate was inhaled once on day 1, and oseltamivir (75 mg) was administered orally twice daily for 5 days. The primary end point was the time to illness alleviation. Results. A total of 996 patients were included in the primary analysis (40-mg Laninamivir octanoate, n = 334; 20-mg Laninamivir octanoate, n = 326; and oseltamivir, n = 336). The median time to illness alleviation in the 40-mg Laninamivir octanoate, 20-mg Laninamivir octanoate, and oseltamivir groups was 73.0, 85.8, and 73.6 h, respectively. The difference between Laninamivir octanoate and oseltamivir was —0.6 h (95% confidence interval, -9.9 to 6.9 h) for the 40-mg group and 12.2 h (95% confidence interval, -1.5 to 17.2 h) for the 20-mg group. The upper limits of the 95% confidence intervals were less than the prespecified noninferiority margin (18 h). The proportion of patients shedding virus at day 3 was significantly lower in the 40-mg Laninamivir octanoate group than in the oseltamivir group (P = .006). Conclusions. A single inhalation of Laninamivir octanoate is effective for the treatment of seasonal influenza, including that caused by oseltamivir-resistant virus, in adults.

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