Pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid of healthy volunteers.
Some subtypes of influenza virus, such as H5N1 and H7N9, cause severe viral pneumonia, for which the intraluminal concentration of the anti-influenza agent in the airway is critical. However, the pharmacokinetics of peramivir, the only available injectable neuraminidase inhibitor formulation, in the airway epithelial lining fluid (ELF) remains unclear. In this study, we aimed to determine the time course of peramivir in the pharyngeal ELF, bronchial ELF and plasma of healthy volunteers using bronchoscopic microsampling technique.



Six healthy volunteers were studied. After baseline plasma sampling, 0.3 g peramivir was intravenously injected over 0.5 h. ELF was obtained from the upper and lower airways using bronchoscopic microsampling at the end of the infusion (0.5 h) and after 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0 h. The concentrations of peramivir in the ELFs and in the plasma were quantified by LC/MS/MS analysis.



The mean maximum concentration (Cmax) in pharyngeal ELF, bronchial ELF and plasma was 1.20 ±0.42, 9.60 ±2.30 and 50.52 ±17.51 ng/ml, respectively. The penetration ratio at Cmaxin pharyngeal and bronchial ELFs was 2.4 and 19.0, respectively. The ratio of the area under the curve from 0 to infinity in pharyngeal and bronchial ELFs was 4.8 and 39.1 mg•min/l, respectively.



The time course of peramivir concentration in the ELFs revealed that concentrations above the 50% inhibitory concentration value of influenza were achieved in the upper and lower airways. Therefore, peramivir could be an important treatment option for influenza viral pneumonia.
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Yohei
Y
Funatsu
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.|Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Sadatomo
S
Tasaka
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Takahiro
T
Asami
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Ho
H
Namkoong
Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan.
Hiroshi
H
Fujiwara
Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan.
Osamu
O
Iketani
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Kazuma
K
Yagi
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Yoshifumi
Y
Kimizuka
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Makoto
M
Ishii
Health Center, Keio University, Tokyo, Japan.
Tomoyasu
T
Nishimura
Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan.
Haruhiko
H
Ogata
Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan.
Satoshi
S
Iwata
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Tomoko
T
Betsuyaku
Center for Infectious Diseases and Infection Control, Keio University School of Medicine, Tokyo, Japan.
Naoki
N
Hasegawa
D000146:Acids, Carbocyclic; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001980:Bronchi / Q000378:metabolism*; D003517:Cyclopentanes / Q000493:pharmacokinetics*; D006146:Guanidines / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007275:Injections, Intravenous; D011446:Prospective Studies
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir