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- W2938995280 abstract "Despite being one of the most commonly prescribed antiepileptic drugs, levetiracetam is marketed in oral and intravenous dosage forms, which are associated to drug-drug interactions and drug-resistant epilepsy (DRE). The purpose of the present study was to assess the potential of the intranasal route to deliver levetiracetam into the brain, due to the particular anatomical features of the nasal cavity. After development and characterization of the drug formulation, a thermoreversible gel loaded with levetiracetam was administered to CD-1 male mice by intranasal route and its pharmacokinetics compared to those observed after intravenous administration. Similar plasma pharmacokinetic profiles were obtained and the intranasal absolute bioavailability was 107.44%, underscoring that a high drug fraction was systemically absorbed. In brain tissue, maximum drug concentrations were 4.48 and 4.02 μg/g (intranasal vs intravenous) and the mean cerebral concentrations were significantly higher after intranasal administration. The percentage of drug targeting efficiency was 182.35% while direct transport percentage was 46.38%, suggesting that almost 50% of levetiracetam undergoes direct nose-to-brain delivery. Complementarily, an in vivo intranasal repeated dose toxicity study was performed and no relevant histopathological alterations were observed. The herein proposed non-invasive and safe intranasal administration route allowed a direct nose-to-brain delivery of levetiracetam and is a promising strategy for the treatment of DRE." @default.
- W2938995280 created "2019-04-25" @default.
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- W2938995280 date "2019-06-01" @default.
- W2938995280 modified "2023-10-17" @default.
- W2938995280 title "Nose-to-brain delivery of levetiracetam after intranasal administration to mice" @default.
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- W2938995280 doi "https://doi.org/10.1016/j.ijpharm.2019.04.047" @default.
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