Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment

[Display omitted] Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to ove...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2022-05, Vol.619, p.121688-121688, Article 121688
Main Authors: Albariqi, Ahmed H., Wang, Yuncheng, Chang, Rachel Yoon Kyung, Quan, Diana H., Wang, Xiaonan, Kalfas, Stefanie, Drago, John, Britton, Warwick J., Chan, Hak-Kim
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animals
Antiviral Agents
COVID-19
COVID-19 Drug Treatment
Dry powder aerosol
Dry Powder Inhalers
Female
Humans
Inhalable ivermectin
Ivermectin
Lactose
Lung - metabolism
Mice
Mice, Inbred BALB C
Pharmacokinetics
Powders - metabolism
Safety
SARS-CoV-2
Spray drying
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2022.121688