# In Vitro and In Vivo Assessment of Pharmacokinetic Profile of Peramivir in the Context of Inhalation Therapy

## TL;DR

This study evaluates how peramivir, an antiviral drug, behaves in the body when inhaled, showing it stays in the lungs and has less systemic spread compared to intravenous use.

## Contribution

The study establishes a preclinical pharmacokinetic platform for inhaled drugs and identifies peramivir as an OCTN2 substrate with favorable lung-targeted delivery.

## Key findings

- Peramivir localizes in alveolar epithelial lining fluid and lung tissue after inhalation with minimal systemic spread.
- In vitro studies show low permeability and no efflux transporter involvement, with uptake confirmed in A549 cells.
- A strong correlation exists between in vitro and in vivo results, supporting inhalation as a viable administration route.

## Abstract

Objective: The 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. Methods: Pharmacokinetic 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. Results: In 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. Conclusions: A 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.