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Abstract Title:

Penetration of oseltamivir and its active metabolite into the brain after lipopolysaccharide-induced inflammation in mice.

Abstract Source:

J Pharm Pharmacol. 2009 Oct;61(10):1397-400. PMID: 19814874

Abstract Author(s):

Shigeru Oshima, Eiichi Nemoto, Mika Kuramochi, Yukiya Saitoh, Daisuke Kobayashi

Article Affiliation:

Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.

Abstract:

OBJECTIVES: Oseltamivir phosphate is used for the treatment of influenza virus infections. Recently, oral intake has been associated with abnormal behaviour. The present study examined the brain penetration of oseltamivir phosphate and oseltamivir carboxylate, its active metabolite, during inflammation. METHODS: Male C57BL/6 mice were given three i.p. injections of lipopolysaccharide (LPS) or saline. We studied the concentration of Evans blue (a marker of blood-brain barrier function) and oseltamivir phosphate and its active metabolite in the brain and plasma. KEY FINDINGS: The brain-to-plasma ratio of Evans blue compared with saline-treated control mice increased significantly with LPS dose. LPS-induced inflammation increased the permeation of drugs through the blood-brain barrier. The concentration of oseltamivir phosphate in both brain and plasma was 2-fold higher in mice treated with LPS than in control mice. Although the plasma concentration of the active carboxylate was not significantly altered by inflammation, the brain concentration was increased 2.7-fold in mice treated with LPS compared with control mice. CONCLUSIONS: Administration of oseltamivir phosphate in the presence of inflammation increased the brain concentration of both parent drug and active metabolite, which may explain the central nervous system side-effects observed with this agent.

Study Type : Animal Study

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