Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study.
Int Immunopharmacol
; 99: 108004, 2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1333527
ABSTRACT
INTRODUCTION:
SARS-CoV-2 replication in cell cultures has been shown to be inhibited by ivermectin. However, ivermectin's low aqueous solubility and bioavailabilityhinders its application in COVID-19 treatment. Also, it has been suggested that best outcomes for this medication can be achieved via direct administration to the lung.OBJECTIVES:
This study aimed at evaluating the safety of a novel ivermectin inhalable formulation in rats as a pre-clinical step.METHODS:
Hydroxy propyl-ß-cyclodextrin(HP-ß-CD) was used to formulate readily soluble ivermectin lyophilized powder. Adult male rats were used to test lung toxicity for ivermectin-HP-ß-CD formulations in doses of 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg for 3 successive days.RESULTS:
The X-ray diffraction for lyophilized ivermectin-HP-ß-CD revealed its amorphous structure that increased drug aqueous solubility 127-fold and was rapidly dissolved within 5 s in saline.Pulmonary administration of ivermectin-HP-ß-CD in dosesof 0.2, 0.4 and 0.8 mg/kgshowed dose-dependent increase in levels of TNF-α, IL-6, IL-13 and ICAM-1 as well as gene expression of MCP-1, protein expression of PIII-NP and serum levels of SP-D paralleled by reduction in IL-10. Moreover, lungs treated with ivermectin (0.2 mg/kg) revealed mild histopathological alterations, while severe pulmonary damage was seen in rats treated with ivermectin at doses of 0.4 and 0.8 mg/kg. However, ivermectin-HP-ß-CD formulation administered in doses of 0.05 and 0.1 mg/kg revealed safety profiles.CONCLUSION:
The safety of inhaledivermectin-HP-ß-CD formulation is dose-dependent. Nevertheless, use of low doses(0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Ivermectin
/
Lung
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Int Immunopharmacol
Journal subject:
Allergy and Immunology
/
Pharmacology
Year:
2021
Document Type:
Article
Affiliation country:
J.intimp.2021.108004
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