Absence of Adverse Effects of Oseltamivir on Sleep: A Double‐Blind, Randomized Study in Healthy Volunteers in Japan

• Published in: Basic & clinical pharmacology & toxicology Vol. 109; no. 4; pp. 309 - 314
• Main Authors: Uchimura, Naohisa, Kuwahara, Hiroo, Kumagai, Yuji, Mishima, Kazuo, Inoue, Yuichi, Rayner, Craig R., Toovey, Stephen, Davies, Brian E., Hosaka, Yoshio, Abe, Masaichi, Prinssen, Eric P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2011; Blackwell
• Subjects: Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - pharmacokinetics; Area Under Curve; Biological and medical sciences; Children; Clinical trials; Cross-Over Studies; Double-Blind Method; EEG; Humans; Influenza; Male; Medical sciences; Oseltamivir; Oseltamivir - adverse effects; Oseltamivir - pharmacokinetics; Pharmacokinetics; Pharmacology. Drug treatments; Phosphate; Side effects; Sleep; Sleep Stages - drug effects; Sleep Stages - physiology; Young Adult; Asia; Japan; Human; Neuraminidase inhibitor; Healthy subject; Enzyme; Toxicity; Enzyme inhibitor; Glycosylases; Oseltamivir; Randomization; Sleep; Exo-α-sialidase; Glycosidases; Secondary effect; Double blind study; Hydrolases; Antiviral; Sleep wake cycle
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2011.00726.x

:  Influenza‐associated neuropsychiatric symptoms include parasomnias such as sleepwalking which is a common sleep disturbance in childhood. Oseltamivir is a widely used antiviral drug for influenza. Recently, sleepwalking‐like events have been reported in patients with influenza receiving oseltamivir. We investigated whether oseltamivir itself has effects on sleep. In this crossover study, healthy Japanese male volunteers were randomized into two treatment groups, each of which comprised two double‐blind 4‐day treatment periods. In the first period, group A received 75 mg oseltamivir (evening dose) on day 3, followed by 75 mg b.i.d. on day 4, and placebo in the second period. Group B received the same treatments, but in reverse order. Polysomnographic assessments were performed on all four nights of each treatment period. Pharmacokinetics were assessed during a 2‐day open‐label phase beginning on day 12. Thirty‐one volunteers aged 20–24 years were enrolled. No volunteer had electroencephalographic abnormalities, and no abnormal behaviour was observed. Sleep parameters measured over the whole night and during early‐ and late sleep periods (first and last thirds of the night) were very similar for oseltamivir and placebo, although the amount of stage 2 sleep in the middle sleep period was slightly greater with oseltamivir. Pharmacokinetics for oseltamivir phosphate in groups A and B were very similar, but for oseltamivir carboxylate, AUC and Cmax values were higher in group B, probably because this group received oseltamivir on the evening of day 11. Oseltamivir was well tolerated. Oseltamivir did not produce clinically relevant changes on nocturnal polysomnographic variables in young Japanese men.