亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Aerosol delivery and spatiotemporal tissue distribution of hydroxychloroquine in rat lung

吸入 呼吸道 药代动力学 羟基氯喹 呼吸系统 药理学 医学 薄壁组织 粘液纤毛清除率 分布(数学) 病理 麻醉 内科学 2019年冠状病毒病(COVID-19) 数学分析 数学 疾病 传染病(医学专业)
作者
Wenhao Xia,Aditya Reddy Kolli,Arkadiusz K. Kuczaj,Justyna Szostak,Sharon Lam,Wei Wen Toh,Anik Purwanti Purwanti,Wei Teck Tan,Raymond T. Ng,Blaine Phillips,Manuel C. Peitsch,Julia Hoeng
出处
期刊:European Journal of Pharmaceutical Sciences [Elsevier BV]
卷期号:194: 106693-106693 被引量:1
标识
DOI:10.1016/j.ejps.2024.106693
摘要

Inhalation enables the delivery of drugs directly to the lung, increasing the retention for prolonged exposure and maximizing the therapeutic index. However, the differential regional lung exposure kinetics and systemic pharmacokinetics are not fully known, and their estimation is critical for pulmonary drug delivery. The study evaluates the pharmacokinetics of hydroxychloroquine in different regions of the respiratory tract for multiple routes of administration. We also evaluated the influence of different inhaled formulations on systemic and lung pharmacokinetics by identifying suitable nebulizers followed by early characterization of emitted aerosol physicochemical properties. The salt- and freebase-based formulations required different nebulizers and generated aerosol with different physicochemical properties. An administration of hydroxychloroquine by different routes resulted in varied systemic and lung pharmacokinetics, with oral administration resulting in low tissue concentrations in all regions of the respiratory tract. A nose-only inhalation exposure resulted in higher and sustained lung concentrations of hydroxychloroquine with a lung parenchyma-to-blood ratio of 386 after 1440 min post-exposure. The concentrations of hydroxychloroquine in different regions of the respiratory tract (i.e., nasal epithelium, larynx, trachea, bronchi, and lung parenchyma) varied over time, indicating different retention kinetics. The spatiotemporal distribution of hydroxychloroquine in the lung is different due to the heterogeneity of cell types, varying blood perfusion clearance mechanisms, and deposition of inhaled aerosol along the respiratory tract. In addition to highlighting the varied lung physiology, these results demonstrate the ability of the lung to retain increased levels of inhaled lysosomotropic drugs. Such findings are critical for the development of future inhalation-based therapeutics, aiming to optimize target site exposure, enable precision medicine, and ultimately enhance clinical outcomes.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
6秒前
8秒前
王佳佳发布了新的文献求助10
10秒前
FashionBoy应助王佳佳采纳,获得10
20秒前
Akim应助饼饼采纳,获得10
27秒前
Jasper应助科研通管家采纳,获得10
35秒前
38秒前
饼饼发布了新的文献求助10
43秒前
59秒前
所所应助阳光的八宝粥采纳,获得30
1分钟前
Yuna96发布了新的文献求助20
1分钟前
1分钟前
脑洞疼应助白桦林泪采纳,获得30
1分钟前
1分钟前
1分钟前
1分钟前
王佳佳发布了新的文献求助10
1分钟前
小二郎应助王佳佳采纳,获得10
1分钟前
晨雾锁阳完成签到 ,获得积分10
1分钟前
科目三应助半分甜采纳,获得10
1分钟前
小白菜完成签到,获得积分10
1分钟前
...完成签到,获得积分10
1分钟前
1分钟前
半分甜发布了新的文献求助10
2分钟前
邓权完成签到,获得积分10
2分钟前
科研通AI5应助jyy采纳,获得10
2分钟前
顾矜应助饼饼采纳,获得10
3分钟前
3分钟前
何为完成签到 ,获得积分10
3分钟前
3分钟前
饼饼发布了新的文献求助10
3分钟前
白桦林泪发布了新的文献求助30
3分钟前
自由橘子完成签到 ,获得积分10
3分钟前
淡定枕头应助huiwanfeifei采纳,获得10
3分钟前
搜集达人应助饼饼采纳,获得10
3分钟前
天天快乐应助白桦林泪采纳,获得10
3分钟前
3分钟前
冬去春来完成签到 ,获得积分10
3分钟前
jyy发布了新的文献求助10
4分钟前
迷路冥幽完成签到,获得积分10
4分钟前
高分求助中
Africanfuturism: African Imaginings of Other Times, Spaces, and Worlds 3000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 2000
Electron microscopy study of magnesium hydride (MgH2) for Hydrogen Storage 1000
Learning to Listen, Listening to Learn: Music Perception and the Psychology of Enculturation 700
Structural Equation Modeling of Multiple Rater Data 700
全球膝关节骨性关节炎市场研究报告 555
Exhibiting Chinese Art in Asia: Histories, Politics and Practices 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3894957
求助须知:如何正确求助?哪些是违规求助? 3438710
关于积分的说明 10808153
捐赠科研通 3163635
什么是DOI,文献DOI怎么找? 1747668
邀请新用户注册赠送积分活动 844087
科研通“疑难数据库(出版商)”最低求助积分说明 787809