Evaluating Drug Deposition Patterns from Turbuhaler® in Healthy and Diseased Lung Models of Preschool Children.
Evaluating Drug Deposition Patterns from Turbuhaler® in Healthy and Diseased Lung Models of Preschool Children.
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发表时间：
2022
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通讯作者：
Singh N
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作者：
Kannan R;Arey R;Przekwas A;Berlinski A;Singh N
使用干粉吸入器（例如 Turbuhaler®）进行儿科口服药物输送的功效取决于测试对象的年龄和健康状况。这些研究的可用临床数据很少，并且很少提供健康状况与局部肺沉积之间的相关性。特别是学龄前儿童的数据和相关性很小。使用新开发的准 3D 全肺模型进行沉积模拟，以分析健康状况对 3 岁儿童 Turbuhaler® 局部肺部沉积的影响。健康肺部模型是根据 CT 扫描数据创建的。通过不同程度地均匀收缩气道来创建囊性纤维化模型。模拟的药物沉积结果根据可用的实验数据进行了验证。结果表明，虽然沉积在肺部的剂量变化较小，但外周：中央 (P/C) 比率受到健康状况和流入变化的强烈影响。对于相同的吸入曲线，与健康对应者相比，重病病例的上述比率降低了约 30%。这表明，在儿童囊性纤维化受试者中，到达外周肺的剂量较低，因此需要较大的治疗剂量。
The efficacy of pediatric oral drug delivery using dry powder inhalers, such as Turbuhaler®, is dependent on the age and health of the test subjects. The available clinical data for these studies is scant and rarely provide correlations between the health condition and the regional lung deposition. In particular, the data and the correlations for pre-school children are minimal. Deposition simulations were performed using the newly developed Quasi-3D whole lung model to analyze the effect of health conditions on the regional lung deposition from the Turbuhaler® in 3-year-old children. The healthy lung model was created from CT scan data. Cystic-fibrosis models were created by uniformly constricting the airways to various degrees. The simulated drug deposition outcomes were validated against the available experimental data. The results show that, while the dose deposited in the lungs exhibits minor variations, the Peripheral:Central (P/C) ratio is strongly affected by both the health condition and the inflow variations. The above ratio is reduced by ~30% for the severely diseased case, compared to its healthy counterpart, for the same inhalation profile. This indicates that lower doses reach the peripheral lung, in pediatric cystic-fibrosis subjects, thus requiring a larger therapeutic dose.