In Vivo Pharmacokinetic Study of Remdesivir Dry Powder for Inhalation in Hamsters
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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 EC 50 s 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 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.
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SciScore for 10.1101/2020.12.22.424071: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Single-dose dry powder insufflation in hamsters: This study was in compliance with the Institutional Animal Care and Use Committee (IACUC; Protocol Number AUP-2019-00254) guidelines at The University of Texas at Austin. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female Syrian hamsters (Charles River, 049LVG) 35-42-days old and weighing between 80 and 130 g (average weight of 102 g) were housed in a 12-hour light/dark cycle with access to food and water ad libitum and were subjected to one week of acclimation to the housing environment. Table 2: Resources
Software and Algorithms Sentences Resources Sulfob… SciScore for 10.1101/2020.12.22.424071: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Single-dose dry powder insufflation in hamsters: This study was in compliance with the Institutional Animal Care and Use Committee (IACUC; Protocol Number AUP-2019-00254) guidelines at The University of Texas at Austin. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female Syrian hamsters (Charles River, 049LVG) 35-42-days old and weighing between 80 and 130 g (average weight of 102 g) were housed in a 12-hour light/dark cycle with access to food and water ad libitum and were subjected to one week of acclimation to the housing environment. Table 2: Resources
Software and Algorithms Sentences Resources Sulfobutylether-beta-cyclodextrin (SBECD, Captisol®) was kindly provided by Ligand Pharmaceuticals, Inc. (San Diego, CA) Ligand Pharmaceuticalssuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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