Berger William E, Gillen Michael, Eckerwall Göran, Uryniak Tom, Trudo Frank J, Lampl Kathy L
Southern California Research Center, Mission Viejo, California, USA.
Allergy Asthma Proc. 2014 Mar-Apr;35(2):134-40. doi: 10.2500/aap.2014.35.3746.
Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov.
6至未满12岁哮喘儿童患者中，通过压力定量吸入器（pMDI）吸入福莫特罗的剂量反应尚未确定。本研究旨在评估接受每日两次（bid）160微克布地奈德治疗的6至未满12岁稳定期哮喘儿童患者，三种福莫特罗pMDI剂量的支气管舒张剂量反应。一项美国多中心五交叉研究，比较了通过pMDI（2.25、4.5和9微克）或干粉吸入器（12微克；活性对照）给予单剂量长效β受体激动剂福莫特罗以及安慰剂的效果，各剂量之间有3至14天的洗脱期。在整个研究过程中，每日两次给予吸入性糖皮质激素布地奈德pMDI 160微克。54名儿科患者（平均年龄9.2岁；平均哮喘病史6.1年）被随机分组。与安慰剂相比，所有福莫特罗剂量组的12小时平均第一秒用力呼气容积（FEV1；曲线下面积）均显著更高（主要疗效）。福莫特罗pMDI 4.5微克和9微克组的12小时平均FEV1显著高于福莫特罗2.25微克组（分别为p = 0.0007和p = 0.0001）。在12小时治疗期内，福莫特罗4.5微克、9微克和12微克剂量组的最大FEV1较安慰剂组和福莫特罗2.25微克剂量组也有显著改善（次要疗效）。福莫特罗2.25微克在12小时给药间隔内未维持支气管舒张作用。未报告严重不良事件。通过尿排泄测定，福莫特罗pMDI在9微克以内一般呈现剂量比例性药代动力学特征。在接受每日两次布地奈德pMDI 160微克维持治疗的6至未满12岁持续性稳定哮喘儿科患者中，单剂量福莫特罗pMDI呈现剂量反应，福莫特罗9微克表现出最大反应。临床试验NCT01136655，www.clinicaltrials.gov 。
