ArticlePharmaceuticals (Basel, Switzerland)2025
In Vitro and In Vivo Assessment of Pharmacokinetic Profile of Peramivir in the Context of Inhalation Therapy.
Article in Pharmaceuticals (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
objectiveThe aim was to evaluate the pharmacokinetics and underlying mechanisms of peramivir, a clinically approved antiviral agent for severe influenza, subsequent to airway inhalation in rats, thereby surmounting the constraints associated with the sole currently available intravenous formulation.
methodsPharmacokinetic and tissue distribution investigations of peramivir were carried out in rats following both intravenous and inhaled administration. In vitro cell models were verified to investigate peramivir's transmembrane transport and cellular uptake across diverse cell systems.
resultsIn vivo, peramivir exhibited restricted permeability, predominantly localizing within the alveolar epithelial lining fluid and lung tissue after inhalation, accompanied by minimal systemic dissemination. In vitro, it manifested low permeability across cell models, with no participation of efflux transporters. Despite the low rate of A549 uptake, the underlying uptake transport mechanism was still revealed. Peramivir was verified as an OCTN2 substrate. A robust correlation was observed between the in vitro and in vivo findings.
conclusionsA preclinical pharmacokinetic platform applicable to inhaled medications was established. Inhalation of peramivir augments exposure at the target site while diminishing systemic exposure, presenting potential therapeutic benefits in terms of efficacy and safety and suggesting it as a favorable alternative administration pathway.
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