Seale J P, Harrison L I
Department of Pharmacology, University of Sydney, NSW, Australia.
Respir Med. 1998 Jun;92 Suppl A:9-15. doi: 10.1016/s0954-6111(98)90212-8.
Reformulation of beclomethasone dipropionate (BDP) in the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane-134a (HFA) gave the opportunity to produce a solution formulation that provides a greater total mass of fine drug particles than the current CFC suspension metered dose inhaler (MDI). The HFA-BDP MDI was studied in three pharmacokinetic trials in asthmatic patients. Serum levels of BDP plus metabolites [total beclomethasone (total BOH) assay] were used to test whether the increased fine particle mass of HFA-BDP would result in improved intrapulmonary deposition and subsequent differences in serum profiles. Serum levels, maximum serum concentrations and area under the serum concentration-time curves of total BOH following both single and multiple doses of HFA-BDP were similar to those obtained with approximately twice the dose of CFC-BDP. The observed lower bioavailability of CFC-BDP compared with HFA-BDP could be explained if most of each inhaled dose from the CFC-BDP MDI was swallowed and absorbed from the gastrointestinal tract, while most of each inhaled dose from the HFA-BDP MDI was absorbed from the lungs. Deposition studies have confirmed this explanation. These results suggest that asthmatic patients can be treated with lower total daily doses of drug from HFA-BDP extrafine aerosol than from CFC-BDP.
将丙酸倍氯米松（BDP）重新配方制成不含氯氟烃（CFC）的推进剂氢氟烷烃-134a（HFA），从而有机会制备出一种溶液制剂，该制剂产生的细药物颗粒总质量比目前的CFC混悬液定量吸入器（MDI）更大。在三项针对哮喘患者的药代动力学试验中对HFA-BDP MDI进行了研究。使用BDP加代谢物的血清水平[总倍氯米松（总BOH）测定]来测试HFA-BDP增加的细颗粒质量是否会导致肺内沉积改善以及随后血清谱的差异。单剂量和多剂量HFA-BDP后总BOH的血清水平、最大血清浓度和血清浓度-时间曲线下面积与使用约两倍剂量CFC-BDP时获得的结果相似。如果来自CFC-BDP MDI的每次吸入剂量大部分被吞咽并从胃肠道吸收，而来自HFA-BDP MDI的每次吸入剂量大部分从肺部吸收，那么观察到的CFC-BDP与HFA-BDP相比生物利用度较低的情况就可以得到解释。沉积研究证实了这一解释。这些结果表明，与CFC-BDP相比，哮喘患者使用HFA-BDP超细气雾剂的每日药物总剂量更低即可得到治疗。
