Pharmacokinetic behavior of peramivir in the plasma and lungs of rats after trans-nasal aerosol inhalation and intravenous injection

Abstract

Peramivir, a neuraminidase inhibitor, was approved globally and is indicated for the treatment of uncomplicated influenza in adults and children. However, the only approved intravenous formulation of peramivir limits its clinical application due to the need for the specialized dosing techniques and increases the risk of contracting influenza virus infection among healthcare professionals when dosing within a short distance to the patient. The purpose of this study was to investigate the pharmacokinetic profile of peramivir in plasma and the lung of rats and to compare the profiles following administration through trans-nasal aerosol inhalation (0.0888, 0.1776, and 0.3552 mg/kg) and intravenous injection (30 mg/kg). The plasma concentration reached the Cmax within 1.0 h (upon inhalation) and decreased at a t1/2 of 6.71 and 10.9 h after inhalation and injection, respectively. The absolute bioavailability of peramivir after inhalation was 78.2 %. Overall, the pharmacokinetic exposure of peramivir in the lungs was higher than that in the plasma after aerosol inhalation. After inhalation, the Cmax of peramivir in the lung was achieved within 1.0 h, and the elimination of the drug was slower than in the case of intravenous injection with t1/2 values 1.81 h for injection and 5.72, 53.5, and 32.1 h for low, middle, and high doses administered through inhalation. The Cmax and AUC0-t values for peramivir in the lungs increased linearly with the increased inhalation dose. The results elucidate the pharmacokinetic process of peramivir after trans-nasal aerosol inhalation to rats and provide useful information for further rational application of this drug formulation.

Keywords

• Peramivir
• Pharmacokinetic profile
• Trans-nasal inhalation
• Lung