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

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

Full text not available from this repository.
Item Type: Article
Official URL:
Journal or Publication Title: International Journal of Pharmaceutics
Volume: 619
Page Range: p. 121688
Date: 10 May 2022
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.ijpharm.2022.121688
ISSN: 03785173
Date Deposited: 08 Jan 2023 22:46

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.

Keywords: COVID-19; Dry powder aerosol; Inhalable ivermectin; Lactose; Pharmacokinetics; Safety; Spray drying.

Albariqi, Ahmed H.
Wang, Yuncheng
Chang, Rachel Yoon Kyung
Quan, Diana H.
Wang, Xiaonan
Kalfas, Stefanie
Drago, John
Britton, Warwick J.
Chan, Hak-Kim
Last Modified: 08 Jan 2023 22:46

Actions (login required)

View Item View Item