Pulmonary Delivery of Favipiravir in Rats Reaches High Local Concentrations without Causing Oxidative Lung Injury or...

Area of Science:

• Pharmacology
• Toxicology
• Respiratory Medicine

Background:

• Oral favipiravir shows efficacy but can cause systemic side effects.
• Pulmonary drug delivery may enhance local concentration and minimize systemic absorption.
• Investigating inhaled favipiravir's safety profile is crucial for potential therapeutic applications.

Purpose of the Study:

• To evaluate the safety of pulmonary favipiravir delivery using a soft-mist inhaler.
• To assess potential deleterious effects on lung, liver, and kidney tissues in healthy rats.
• To determine if inhaled favipiravir causes cardiac, hepatorenal, or oxidative stress.

Main Methods:

• Wistar albino rats received daily inhaled favipiravir (1-10 mg/kg) or saline for five consecutive days.
• Cardiac rhythm, blood cell counts, and serum biomarkers (liver enzymes, kidney function markers) were analyzed.
• Lung tissue was examined for oxidative stress markers (malondialdehyde, glutathione) and myeloperoxidase activity.

Main Results:

• Inhaled favipiravir did not affect cardiac rhythm or blood cell counts.
• No significant changes were observed in liver enzymes (ALT, AST) or kidney function markers (BUN, creatinine, urea, uric acid).
• Pulmonary administration did not induce oxidative lung injury, with normal malondialdehyde, myeloperoxidase, and glutathione levels.

Conclusions:

• Pulmonary delivery of favipiravir via soft-mist inhaler is safe in healthy rats.
• This route achieves high local lung concentrations without systemic toxicity or organ damage.
• Inhaled favipiravir presents a promising alternative for localized respiratory treatment with an improved safety profile.