瑞德西韦吸入用干粉在仓鼠体内的药代动力学研究。

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

作者信息

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

机构信息

Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, Austin, TX 78723, USA.

出版信息

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

DOI:10.1016/j.ijpx.2021.100073

PMID:34977555

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8683664/

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 ECs 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 with shorter T 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.

摘要

吸入用瑞德西韦干粉剂此前是采用薄膜冷冻法（TFF）研发的。一项在仓鼠身上开展的单剂量24小时药代动力学研究表明，通过肺部给药的TFF瑞德西韦在20小时内可使血浆中的瑞德西韦和GS-441524水平高于已报道的瑞德西韦和GS-441524（在人上皮细胞中的）有效浓度。干粉吸入后GS-4412524的半衰期约为7小时，这表明给药方案应为每日两次。尽管瑞德西韦-磺丁基醚-β-环糊精（80/20 w/w）制剂在肺部对瑞德西韦和GS-4412524的吸收更快且更多，但瑞德西韦-亮氨酸（80/20 w/w）的GS-441524的C更高、T更短且AUC更低，这表明达到针对新型冠状病毒的高有效浓度所需的总药物暴露量更低。总之，吸入用瑞德西韦干粉剂有望成为治疗新冠肺炎的一种替代剂型。