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In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.12.22.424071
ABSTRACT
Remdesivir dry powder for inhalation was previously developed using thin film freezing (TFF). A single dose 24 hour pharmacokinetic study in hamsters, a small animal model for SARS-CoV-2, demonstrated that pulmonary delivery of TFF remdesivir can achieve plasma remdesivir and GS-441524 levels higher than the reported EC50s of both remdesivir and GS441524 (in human epithelial cells) over 20 hours. The half life of GS4412524 following dry powder insufflation was about 7 hours, suggesting the dosing regimen would be twice daily administration. Although the remdesivir-Captisol (80/20 w/w) formulation showed faster and greater absorption of remdesivir and GS-4412524 in the lung, remdesivir-leucine (80/20 w/w) exhibited a greater Cmax with shorter Tmax and lower AUC of GS441524, indicating lower total drug exposure is required to achieve a high effective concentration against SAR-CoV-2. In conclusion, remdesivir dry powder for inhalation would be a promising alternative dosage form for the treatment of COVID-19 disease.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Adenomatous Polyposis Coli
/
COVID-19
Language:
English
Year:
2020
Document Type:
Preprint
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