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Pulmonary Delivery of Favipiravir in Rats Reaches High Local Concentrations without Causing Oxidative Lung Injury or
Ozlem Akbal-Dagistan1, Mustafa Sevim2, Leyla Semiha Sen2
1Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Türkiye.
Abstract:
Favipiravir displays a rapid viral clearance, a high recovery rate and broad therapeutic safety; however, its oral administration was associated with systemic side effects in susceptible patients. Considering that the pulmonary route could provide a high drug concentration, and a safer application with less absorption into systemic circulation, it was aimed to elucidate whether favipiravir delivered via soft-mist inhaler has any deleterious effects on lung, liver and kidney tissues of healthy rats. Wistar albino rats of both sexes (n = 72) were placed in restrainers, and were given either saline or favipiravir (1, 2.5, 5 or 10 mg/kg in 1 mL saline) by inhalation within 2 min for 5 consecutive days. On the 6th day, electrocardiographic recording was obtained, and cardiac blood and lung tissues were collected. Favipiravir did not alter cardiac rhythm, blood cell counts, serum levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, urea or uric acid, and did not cause any significant changes in the pulmonary malondialdehyde, myeloperoxidase activity or antioxidant glutathione levels. Our data revealed that pulmonary use of favipiravir via soft-mist inhaler enables a high local concentration compared to plasma without oxidative lung injury or cardiac or hepatorenal dysfunction.
Insights
Pulmonary administration of favipiravir via soft-mist inhaler in rats showed no adverse effects on lung, liver, or kidney tissues. This delivery method may offer a safer alternative with high local drug concentration and reduced systemic absorption.
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.
