Remdesivir dry powder inhalation formulation, pharmacokinetic study in hamsters

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Currently, remdesivir is only available as a lyophilized powder for reconstitution and intravenous
53 infusion and concentrate solution for dilution and intravenous infusion. The current dosage forms are limited to only hospitalized patients, excluding outpatient care. Therefore, alternative dosage forms of remdesivir for different routes of administration are necessary to improve the accessibility of the drug for patients besides those which are critically ill.

Remdesivir dry powder for inhalation was previously developed using thin film freezing (TFF) using excipients (e.g., Captisol®, mannitol, lactose, leucine) at 80/20 (w/w) ratio showed optimal aerosol performance for pulmonary delivery. A pharmakokinetic study in hamsters was reported here [1]. 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, the parent nucleoside analogue core of remdesivir, levels higher than the reported EC50s of both remdesivir and GS-441524 (in human epithelial cells) over 20 hours. The half-life of GS-4412524 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 GS-441524, 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.

See also:

[1] Sawittree Sahakijpijarn, Chaeho Moon, Zachary N. Warnken, Esther Y. Maier, Jennie E. DeVore,
Dale J. Christensen, John J. Koleng and Robert O. Williams III (2020) In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters.


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