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• W2034461950 abstract "Oseltamivir (Tamiflu, Roche, Nutley, NJ), an ester-type prodrug of the anti-influenza drug Ro 64-0802 (oseltamivir carboxylate), has been reported to be associated with neuropsychiatric side effects, which are likely to be caused by distribution of oseltamivir and/or its metabolite into the central nervous system. Enhanced toxicity and brain distribution of oseltamivir in unweaned rats led us to hypothesize that the low level of distribution of oseltamivir and/or Ro 64-0802 in adult brain was caused by the presence of a specific efflux transporter at the blood-brain barrier. We examined the possible role of P-glycoprotein (P-gp) as the determinant of brain distribution of oseltamivir and Ro 64-0802 both in vitro using LLC-GA5-COL150 cells, which overexpress human multidrug resistance protein 1 P-gp on the apical membrane, and in vivo using mdr1a/1b knockout mice. The permeability of oseltamivir in the basal-to-apical direction was significantly greater than that in the opposite direction. The directional transport disappeared on addition of cyclosporin A, a P-gp inhibitor. The brain distribution of oseltamivir was increased in mdr1a/1b knockout mice compared with wild-type mice. In contrast, negligible transport of Ro 64-0802 by P-gp was observed in both in vitro and in vivo studies. These results show that oseltamivir, but not Ro 64-0802, is a substrate of P-gp. Accordingly, low levels of P-gp activity or drug-drug interactions at P-gp may lead to enhanced brain accumulation of oseltamivir, and this may in turn account for the central nervous system effects of oseltamivir observed in some patients." @default.
• W2034461950 created "2016-06-24" @default.
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• W2034461950 date "2007-10-16" @default.
• W2034461950 modified "2023-09-30" @default.
• W2034461950 title "Oseltamivir (Tamiflu) Efflux Transport at the Blood-Brain Barrier via P-Glycoprotein" @default.
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• W2034461950 doi "https://doi.org/10.1124/dmd.107.017699" @default.
• W2034461950 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17940134" @default.
• W2034461950 hasPublicationYear "2007" @default.
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