In vivo pharmacokinetic study of remdesivir dry powder for inhalation in hamsters

Sawittree Sahakijpijarn; Chaeho Moon; Zachary N Warnken; Esther Y Maier; Jennie E DeVore; Dale J Christensen; John J Koleng; Robert O Williams 3rd

doi:10.1016/j.ijpx.2021.100073

In vivo pharmacokinetic study of remdesivir dry powder for inhalation in hamsters

Int J Pharm X. 2021 Feb 27:3:100073. doi: 10.1016/j.ijpx.2021.100073. eCollection 2021 Dec.

Authors

Sawittree Sahakijpijarn¹, Chaeho Moon¹, Zachary N Warnken¹, Esther Y Maier², Jennie E DeVore², Dale J Christensen³, John J Koleng³, Robert O Williams 3rd¹

Affiliations

¹ Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
² Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, Austin, TX 78723, USA.
³ TFF Pharmaceuticals, Inc., Austin, TX 78746, USA.

Abstract

Remdesivir dry powder for inhalation was previously developed using thin film freezing (TFF). A single-dose 24-h pharmacokinetic study in hamsters 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 h. The half-life of GS-4412524 following dry powder insufflation was about 7 h, 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 C_max with shorter T_max 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.

Keywords: COVID-19; Dry powder for inhalation; Pharmacokinetics; Remdesivir; SARS-CoV-2; Thin film freezing.