University of Montpellier, Montpellier, France.
Clin Pharmacokinet. 2009;48(6):347-58. doi: 10.2165/00003088-200948060-00001.
Foster is a fixed combination of beclometasone dipropionate/formoterol (BDP/F). It is formulated as an extra-fine solution and delivered via a pressurized metered-dose inhaler (pMDI) using a hydrofluoroalkane (HFA) propellant. The aims of this study were to compare the systemic exposure to BDP, to its active metabolite beclometasone-17-monopropionate (B17MP) and to formoterol after administration of BDP/F versus separate administration of a chlorofluorocarbon (CFC) formulation of BDP and formoterol HFA, and to explore a possible relationship between pharmacokinetic and pharmacodynamic findings.
In this open-label, crossover, placebo-controlled study, 12 healthy male subjects received a single dose of BDP/F 400 microg/24 microg (four inhalations of Foster BDP/F 100 microg/6 microg), single doses of BDP CFC 1000 microg (four inhalations of Becotide Forte 250 microg) plus formoterol 24 microg (four inhalations of Atimos 6 microg) via separate MDIs, or placebo. Continuous pharmacokinetic variables for BDP, B17MP, formoterol, cortisol and potassium were evaluated. Cardiovascular effects, peak flow measurements and tolerability were also examined.
Exposure to BDP was not significantly different between active treatment arms, but lower systemic exposure to B17MP was observed with the fixed combination than with the separate components (area under the plasma concentration-time curve [AUC] from time zero to infinity [AUC(infinity)] 5280 vs 8120 pg.h/mL; p = 0.001). Despite a lower total systemic exposure to B17MP with the fixed combination, B17MP plasma concentrations during the first 30 minutes after administration, indicative of pulmonary absorption, were 86% higher with BDP/F than with the separate components (AUC from 0 to 30 minutes [AUC(30 min)] 353 vs 190 pg x h/mL; p = 0.003). Twenty-four-hour serum cortisol concentrations were significantly higher with BDP/F than with BDP and formoterol administered separately (2.26 vs 1.90 microg x h/mL; p < 0.01). No significant differences in the pharmacokinetic parameters of formoterol and no clinically relevant differences in serum potassium and cardiovascular or spirometric parameters were observed between the treatments. Both active treatments were well tolerated.
These pharmacokinetic data show that with a BDP dose from Foster that is 2.5 times less than a BDP dose from Becotide Forte, pulmonary absorption is 86% higher; however, systemic exposure is 35% lower, resulting in less cortisol suppression for a similar BDP dosage.
辅舒酮为丙酸倍氯米松/福莫特罗（BDP/F）的固定复方制剂。它被制成超细溶液，并通过使用氢氟烷烃（HFA）推进剂的压力计量吸入器（pMDI）来给药。本研究的目的是比较在给予丙酸倍氯米松/福莫特罗（BDP/F）与分别给予氟利昂（CFC）配方的丙酸倍氯米松和福莫特罗 HFA 后，BDP、其活性代谢物倍氯米松-17-丙酸酯（B17MP）和福莫特罗的全身暴露情况，并探讨药代动力学和药效学发现之间的可能关系。
在这项开放标签、交叉、安慰剂对照研究中，12 名健康男性受试者接受了单剂量的辅舒酮 400μg/24μg（4 吸辅舒酮 100μg/6μg）、单剂量的氟替卡松 CFC 1000μg（4 吸倍氯米松福莫特罗 250μg）加福莫特罗 24μg（4 吸信必可都保 6μg），或安慰剂。评估了 BDP、B17MP、福莫特罗、皮质醇和钾的连续药代动力学变量。还检查了心血管效应、峰值流量测量和耐受性。
与活性治疗组相比，BDP 的全身暴露无显著差异，但固定组合的 B17MP 全身暴露低于单独成分（从时间零到无穷大的血浆浓度-时间曲线下面积[AUC（无穷大）]5280 与 8120 pg.h/mL；p=0.001）。尽管固定组合的 B17MP 总全身暴露较低，但在给药后 30 分钟内，指示肺吸收的 B17MP 血浆浓度，BDP/F 比单独成分高 86%（AUC 从 0 到 30 分钟[AUC（30 分钟）]353 与 190 pg x h/mL；p=0.003）。与单独给予 BDP 和福莫特罗相比，BDP/F 给药后 24 小时血清皮质醇浓度显著升高（2.26 与 1.90 μg x h/mL；p<0.01）。在福莫特罗的药代动力学参数方面未观察到显著差异，在血清钾和心血管或肺量计参数方面未观察到临床相关差异。两种活性治疗均耐受良好。
这些药代动力学数据表明，在给予辅舒酮的 BDP 剂量是倍氯米松福莫特罗 2.5 倍的情况下，肺吸收增加 86%；然而，全身暴露降低 35%，从而在相似的 BDP 剂量下，皮质醇抑制减少。
