Farkas Árpád, Tomisa Gábor, Szénási Georgina, Füri Péter, Kugler Szilvia, Nagy Attila, Varga János, Horváth Alpár
Centre for Energy Research, Konkoly Thege M. út 29-33, Budapest 1121, Hungary.
Chiesi Hungary Kft., Dunavirág utca 2, Budapest 1138, Hungary.
Int J Pharm X. 2023 Jun 22;6:100192. doi: 10.1016/j.ijpx.2023.100192. eCollection 2023 Dec 15.
The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.
药物在气道中的沉积量尤其取决于吸入动作和呼吸参数。本研究的目的是量化药物吸入前肺排空对肺内药物剂量的影响。招募了30名健康成年人。在他们通过六种不同的排空型干粉吸入器（DPI）吸入时，记录其呼吸曲线，吸入时不呼气，且分别在舒适呼气或用力呼气后进行记录。相应的喷出剂量和气溶胶粒径分布数据来自文献。使用随机肺模型来估算沉积剂量。一般来说，用力呼气会导致流速和吸入空气量增加。对于肺剂量与流速呈正相关的药物（例如信必可都保®：相对增加6.7%，布地奈德福莫特罗混合粉吸入剂®：相对增加9.2%），流速增加会导致平均肺内药物剂量增加。对于肺剂量与流速呈负相关的药物（除上述两种药物外的所有研究药物），肺排空会导致平均肺内药物剂量增加（富里酸®增加2.7%）、几乎不变（思力华®、Relvar®、Bretaris®）以及减少（昂润®减少6.6%）。值得注意的是，个体间存在显著差异，并且每种药物的肺内剂量在一些受试者中会增加。总之，肺内药物剂量的变化取决于肺排空程度，但也因吸入器和药物而异。只有考虑到上述特异性，用力呼气才有助于增加肺内药物剂量。
