tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2012 Apr 23. [Epub ahead of print]
Intrapulmonary Distribution and Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, After a Single Inhaled Administration of its Prodrug, Laninamivir Octanoate, in Healthy Volunteers.
Ishizuka H, Toyama K, Yoshiba S, Okabe H, Furuie H.
Source
Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Abstract
A single inhaled dose of laninamivir octanoate (LO), a long-acting neuraminidase inhibitor, exhibits efficacy to treat 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 in adult healthy volunteers. Subgroups of five subjects each underwent bronchoalveolar lavage (BAL) at 4, 8, 24, 48, 72, 168, and 240 h following a single inhaled administration of LO (40 mg). Plasma, BAL fluid and alveolar macrophage (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 the subsequent BAL fluid samples were separately determined to explore the drug distribution in airways. Mean laninamivir concentrations in ELF calculated using the first and the subsequent BAL fluids collected 4 h after inhaled administration were 8.57 and 2.40 μg/mL, respectively. Laninamivir in ELF decreased with a longer half-life than that in plasma and notably exceeded the 50% inhibitory concentrations for viral neuraminidase at all time points examined up to 240 h after the inhalation. Laninamivir exposure in ELF from the first BAL samples was 3.2-times higher than that from the subsequent BAL samples. ELF concentration profiles of laninamivir support its long lasting effect to treat patients with influenza virus infection by a single inhaled administration.
PMID:
22526307
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22526307
Intrapulmonary Distribution and Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, After a Single Inhaled Administration of its Prodrug, Laninamivir Octanoate, in Healthy Volunteers.
Ishizuka H, Toyama K, Yoshiba S, Okabe H, Furuie H.
Source
Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Abstract
A single inhaled dose of laninamivir octanoate (LO), a long-acting neuraminidase inhibitor, exhibits efficacy to treat 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 in adult healthy volunteers. Subgroups of five subjects each underwent bronchoalveolar lavage (BAL) at 4, 8, 24, 48, 72, 168, and 240 h following a single inhaled administration of LO (40 mg). Plasma, BAL fluid and alveolar macrophage (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 the subsequent BAL fluid samples were separately determined to explore the drug distribution in airways. Mean laninamivir concentrations in ELF calculated using the first and the subsequent BAL fluids collected 4 h after inhaled administration were 8.57 and 2.40 μg/mL, respectively. Laninamivir in ELF decreased with a longer half-life than that in plasma and notably exceeded the 50% inhibitory concentrations for viral neuraminidase at all time points examined up to 240 h after the inhalation. Laninamivir exposure in ELF from the first BAL samples was 3.2-times higher than that from the subsequent BAL samples. ELF concentration profiles of laninamivir support its long lasting effect to treat patients with influenza virus infection by a single inhaled administration.
PMID:
22526307
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22526307