Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model
Pharmacokinetic/pharmacodynamic aspects of aerosol therapy using glucocorticoids as a model
复制标题
DOI：
10.1002/j.1552-4604.1997.tb04262.x
复制
发表时间：
1997-10-01
影响因子：
2.9
通讯作者：
GonzalezRothi, RJ
中科院分区：
文献类型：
--
作者：
Hochhaus, G;Mollmann, H;GonzalezRothi, RJ
糖皮质激素在哮喘治疗中主要以气雾剂的形式处方，以实现高的肺部效应，减少全身溢出和显著的肺部选择性。各种药代动力学参数对于确定肺部选择性可能是重要的。本文的目的是提供一种实践相关的理论方法，将这些参数对肺靶向的重要性作为一种工具，使用药代动力学/药效学建模。应用的肺部药代动力学/药效学模型显示，除了公认的参数（如全身清除率、口服生物利用度和肺部沉积效率）外，其他因素（如肺部释放（溶出）速率和剂量）也相关。然而，分布容积（对于不经历昼夜节律的效应参数）和给定糖皮质激素的受体亲和力对于实现肺靶向并不重要。
Glucocorticoids are predominantly prescribed in asthma therapy as aerosols to achieve high pulmonary effects with reduced systemic spill-over and pronounced pulmonary selectivity A variety of pharmacokinetic parameters are potentially important for determining pulmonary selectivity. The intent of this article, is to provide a practice-relevant theoretical approach to put the importance of these parameters on pulmonary targeting using pharmacokinetic/pharmacodynamic modeling as a tool in perspective. The applied pulmonary pharmacokinetic/pharmacodynamic model revealed that, in addition to recognized parameters such as systemic clearance, oral bioavailability, and efficiency of pulmonary deposition, other factors, such as the pulmonary release (dissolution) rate and dose, are relevant. However, the volume of distribution (for effect parameters not undergoing a diurnal rhythm) and the receptor affinity of a given glucocorticoid are not important for achieving lung targeting.