Regional lung targeting with a fluticasone/salmeterol aerosol using a bolus breath hold method of the PreciseInhale® system: A first evaluation in humans

丙酸氟替卡松 气溶胶 丸(消化) 医学 计量吸入器 吸入器 药理学 沙美特罗 吸入 麻醉 哮喘 化学 内科学 有机化学
作者
Per Gerde,Carl-Olof Sjöberg,Helen Bäckroos,Joakim Englund,Marit Wangheim,Helena Litorp
出处
期刊:European Journal of Pharmaceutical Sciences [Elsevier BV]
卷期号:196: 106742-106742
标识
DOI:10.1016/j.ejps.2024.106742
摘要

In development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation. The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures. Aerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles. Two main comparisons were made by measuring the systemic PK response:I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung. When one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57% higher Cmax in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23% higher AUC24 in the peripheral lung with no noticeable elevation around Cmax. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as tmax, Cmax, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.
最长约 10秒,即可获得该文献文件

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
共享精神应助chun采纳,获得10
1秒前
小马甲应助mr.pork采纳,获得10
1秒前
清新的小懒猪完成签到,获得积分10
2秒前
酷波er应助科研通管家采纳,获得10
2秒前
2秒前
充电宝应助科研通管家采纳,获得10
2秒前
情怀应助科研通管家采纳,获得10
3秒前
科研通AI5应助科研通管家采纳,获得10
3秒前
逆时针应助科研通管家采纳,获得10
3秒前
Owen应助科研通管家采纳,获得50
3秒前
CipherSage应助科研通管家采纳,获得10
3秒前
圆锥香蕉应助科研通管家采纳,获得20
3秒前
乐乐应助科研通管家采纳,获得10
3秒前
天天快乐应助科研通管家采纳,获得10
3秒前
3秒前
圆锥香蕉应助科研通管家采纳,获得20
3秒前
3秒前
科研通AI2S应助科研通管家采纳,获得10
3秒前
qsy发布了新的文献求助10
5秒前
懵懂的半蕾完成签到,获得积分10
5秒前
Fengliguantou发布了新的文献求助30
5秒前
xunxunmimi完成签到,获得积分10
5秒前
6秒前
科目三应助乐观紫采纳,获得10
7秒前
我是小短腿的妹妹完成签到,获得积分20
8秒前
lily完成签到,获得积分10
8秒前
感谢有你发布了新的文献求助10
10秒前
wh2740完成签到,获得积分10
11秒前
SHAO应助可乐冰淇淋采纳,获得30
14秒前
14秒前
脑洞疼应助JUdy采纳,获得10
16秒前
何白发布了新的文献求助10
16秒前
Lu发布了新的文献求助10
17秒前
hugdoggy完成签到,获得积分10
19秒前
19秒前
桃子发布了新的文献求助30
22秒前
23秒前
Liufgui给风之星的求助进行了留言
23秒前
24秒前
Lucas应助桔子采纳,获得30
26秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989115
求助须知:如何正确求助?哪些是违规求助? 3531367
关于积分的说明 11253688
捐赠科研通 3269986
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882078
科研通“疑难数据库(出版商)”最低求助积分说明 809105