MacGregor T R, ZuWallack R, Rubano V, Castles M A, Dewberry H, Ghafouri M, Wood C C
Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA.
St. Francis Hospital Medical Center, Hartford, Connecticut, USA.
Clin Transl Sci. 2016 Apr;9(2):105-13. doi: 10.1111/cts.12387. Epub 2016 Mar 6.
The propellant-free Combivent Respimat Soft Mist Inhaler (CVT-R) was developed to replace the chlorofluorocarbon-propelled Combivent metered-dose inhaler (CVT-MDI). This steady-state pharmacokinetic (PK) substudy evaluated drug lung-delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well-controlled population PK analyses. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (C(max)), and minimum observed plasma concentration (C(min)) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT-R was proportional to ex-mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT-R was half that in the CVT-MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT-R delivers drug more efficiently to the lung than CVT-MDI.
不含推进剂的可必特软雾吸入器（CVT-R）是为取代含氯氟烃推进的可必特定量气雾剂（CVT-MDI）而研发的。这项稳态药代动力学（PK）子研究利用两项III期安全性和有效性试验的数据，评估了药物肺部递送效率。PK参数通过严格控制的群体PK分析获得。血浆浓度-时间曲线下面积（AUC）、观察到的最大血浆浓度（C(max)）和观察到的最小血浆浓度（C(min)）显示，通过CVT-R递送的异丙托溴铵和沙丁胺醇的全身暴露量与经口器递送剂量成正比。尽管CVT-R中异丙托溴铵的标示剂量是CVT-MDI中的一半，但全身暴露量相当。未证明异丙托溴铵和可必特软雾吸入器药物成分之间存在PK相互作用。单独使用异丙托溴铵导致的暴露量与异丙托溴铵和沙丁胺醇联合使用时相似。这些结果表明，CVT-R比CVT-MDI能更有效地将药物递送至肺部。
