In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters

sahakijpijarn, s.; Moon, C.; Warnken, Z. N.; Maier, E.; DeVore, J. E.; Christensen, D. J.; Koleng, J. J.; Williams, R. O.

doi:10.1101/2020.12.22.424071

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bioRxiv · 10.1101/2020.12.22.424071

In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters

sahakijpijarn, s.·Moon, C.·Warnken, Z. N.·Maier, E.·DeVore, J. E.·Christensen, D. J.·Koleng, J. J.·Williams, R. O.

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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 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(R) (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.

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sahakijpijarn, s., Moon, C., Warnken, Z. N., Maier, E., DeVore, J. E., Christensen, D. J., Koleng, J. J., Williams, R. O.. 2020-12-23. In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters. https://doi.org/10.1101/2020.12.22.424071

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