Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark.
Br J Clin Pharmacol. 2013 Apr;75(4):1081-8. doi: 10.1111/j.1365-2125.2012.04459.x.
The fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 μg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 μg vs. the free combination of BDP and formoterol pMDIs in asthmatic children.
Children aged 5-11 years old inhaled BDP 200 μg and formoterol 24 μg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,∞), AUC(0,0.5 h, Cmax , tmax , t1/2 ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored.
Twenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml(-1) h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml(-1) h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related.
BDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children.
倍氯米松（BDP）和福莫特罗压力定量吸入剂（pMDI）（Foster ® ，Chiesi Farmaceutici）的固定组合正在开发较低的强度（BDP/福莫特罗：50/6μg），以提供适当的剂量哮喘儿童。本工作的目的是研究单吸入 Foster ® pMDI 50/6μg 后倍氯米松-17-丙酸酯（B17MP，BDP 的活性代谢物）和福莫特罗的全身生物利用度与哮喘儿童中 BDP 和福莫特罗 pMDI 的自由组合。
5-11 岁的儿童分别以固定组合和自由组合方式吸入倍氯米松 200μg 和福莫特罗 24μg，进行一项开放标签、随机、两向交叉单剂量研究。在给药前至给药后 8 小时采集血样进行药代动力学评估（AUC（0，t）、AUC（0，∞）、AUC（0，0.5h，Cmax ，tmax ，t1/2 ）。药效学包括心率、血浆钾、尿糖和皮质醇排泄。监测呼气峰流速和不良反应。
20 名受试者可评估。固定组合给药时 B17MP 和福莫特罗的全身暴露量未超过自由组合：B17MP AUC（0，t）（pg·ml（-1）·h）比值检验：参考（90%CI），0.81（0.697，0.948）和福莫特罗 AUC（0，t）（pg·ml（-1）·h）比值检验：参考 0.97（0.85，1.10）。所有药代动力学和药效学终点均显示试验药物不具有优越性。发生 1 例不良反应（眩晕），但不认为与治疗有关。
在 5-11 岁哮喘儿童中，BDP 和福莫特罗的药代动力学和药效学作用在给予两种活性药物的固定组合与自由组合后不具有优越性。
