Preparation and comprehensive preclinical study of Peramivir inhalation solution: Achieving accurate drug delivery

Peramivir, a Neuraminidase inhibitor used for influenza A or B treatment, is currently marketed in the form of injections globally. However, Peramivir injections result in widespread systemic distribution, with only 3-9 % of the drug reaching the nasal cavity and pharyngeal mucus (key sites of action). In contrast, inhaled formulations can directly reach the site of absorption or action, leading to rapid onset of effect. This approach circumvents the first-pass hepatic metabolism, reduces the dosage required, minimizes systemic exposure, and may mitigate or avoid certain adverse drug reactions. It is noteworthy that no Peramivir inhalation solution (PIS) products are currently available globally. In this study, we focused on the reformulation of Peramivir from intravenous to inhalation administration, conducting comprehensive research on its toxicity, tissue distribution, pharmacokinetics, and pharmacodynamics. We demonstrated that PIS, compared to intravenous administration, exhibited heightened local drug exposure in lung tissues, longer exposure duration, slower elimination, and exhibited good tolerability without specific safety concerns.