College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA.
Pharm Res. 2017 Dec;34(12):2541-2556. doi: 10.1007/s11095-017-2235-y. Epub 2017 Aug 10.
The ability of two semi-mechanistic simulation approaches to predict the systemic pharmacokinetics (PK) of inhaled corticosteroids (ICSs) delivered via dry powder inhalers (DPIs) was assessed for mometasone furoate, budesonide and fluticasone propionate.
Both approaches derived the total lung doses and the central to peripheral lung deposition ratios from clinically relevant cascade impactor studies, but differed in the way the pulmonary absorption rate was derived. In approach 1, the rate of in vivo drug dissolution/absorption was predicted for the included ICSs from in vitro aerodynamic particle size distribution and in vitro drug solubility estimates measured in an in vivo predictive dissolution medium. Approach 2 derived a first order absorption rate from the mean dissolution time (MDT), determined for the test formulations in an in vitro Transwell based dissolution system.
Approach 1 suggested PK profiles which agreed well with the published pharmacokinetic profiles. Similarly, within approach 2, input parameters for the pulmonary absorption rate constant derived from dissolution rate experiments were able to reasonably predict the pharmacokinetic profiles published in literature.
Approach 1 utilizes more complex strategies for predicting the dissolution/absorption process without providing a significant advantage over approach 2 with regard to accuracy of in vivo predictions.
评估两种半机械模拟方法预测干粉吸入器（DPI）给药的吸入性皮质类固醇（ICS）全身药代动力学（PK）的能力，所涉及的 ICS 有糠酸莫米松、布地奈德和丙酸氟替卡松。
两种方法均从临床相关级联撞击器研究中得出总肺剂量和中央至外周肺沉积比，但推导肺吸收速率的方式不同。在方法 1 中，从包括的 ICS 的体内空气动力学粒径分布和体内预测性溶解介质中测量的体外药物溶解度估计值，预测体内药物溶解/吸收的速率。方法 2 从测试配方在体外 Transwell 溶解系统中确定的平均溶解时间（MDT）得出一阶吸收速率。
方法 1 提出的 PK 曲线与已发表的药代动力学曲线吻合良好。同样，在方法 2 中，从溶解速率实验中推导的肺吸收速率常数的输入参数能够合理地预测文献中发表的药代动力学曲线。
方法 1 利用更复杂的策略来预测溶解/吸收过程，但在体内预测的准确性方面并没有优于方法 2。
