Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ul...Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for simultaneous determination of fluticasone propionate and salmeterol xinofoate in human plasma. Following a simple SPE sample extraction in 96-well plate format, chromatography was performed on a Waters ACQUITY UPLC BEH C 18 column （1.7 μm, 50 min×2.1 mm） with mobile phase consisting of 100% MeOH and 0.1% NH4OH in water on a gradient program at flow rate of 0.5 mL/min. Detection of analytes and internal standards was accomplished using multiple reaction monitoring （MRM） of precursor〉product ion pairs of m/z 501.4〉313.2 （fluticasone propionate）, 506.4〉293.3 （fluticasone propionate-d5）, 416.4〉232.1 （salmeterol xinofoate） and 419.3〉235.2 （salmeterol-d3）. The assay range was 2.50-500 pg/mL for both analytes, and a 1/x2 weighted linear regression model was used. The inter-assay accuracy and precision of the method were within ±8.6%. The recoveries from 0.30 mL of plasma were greater than 51.0% and 54.6% for fluticasone propionate and salmeterol, respectively, and the results were consistent across low, middle and high concentration levels. The method was validated following FDA, EMA and CFDA （China Food and Drug Administration）＇s guidance on bioanalysis and then successfully applied to support a clinical study in healthy Chinese subjects following inhaled administration of a single combination of fluticasone propionate/salmeterol （250 μg/50 μg）.展开更多
Background:Despite the recommendation of inhaled corticosteroids(ICSs)plus long-acting beta 2-agonist(LABA)and leukotriene receptor antagonist(LTRA)or ICS/LTRA as stepwise approaches in asthmatic children,there is a l...Background:Despite the recommendation of inhaled corticosteroids(ICSs)plus long-acting beta 2-agonist(LABA)and leukotriene receptor antagonist(LTRA)or ICS/LTRA as stepwise approaches in asthmatic children,there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years.This study aimed to compare the safety and efficacy of salmeterol/fluticasone(SFC)vs.montelukast(MON),or combination of montelukast and fluticasone(MFC)in children and adolescents aged 4 to 18 years with bronchial asthma.Methods:A systematic search was conducted in MEDLINE,EMBASE,the Cochrane Library,China BioMedical Literature Database,Chinese National Knowledge Infrastructure,VIP Database for Chinese Technical Periodical,and Wanfang for randomized controlled trials(RCTs)published from inception to May 24,2021.Interventions are as follows:SFC vs.MON,or combination of MFC,with no limitation of dosage or duration.Primary and secondary outcome measures were as follows:the primary outcome of interest was the risk of asthma exacerbation.Secondary outcomes included risk of hospitalization,pulmonary function,asthma control level,quality of life,and adverse events(AEs).A random-effects(I^(2)≥50%)or fixed-effects model(I^(2)<50%)was used to calculate pooled effect estimates,comparing the outcomes between the intervention and control groups where feasible.Results:Of the 1006 articles identified,21 studies met the inclusion criteria with 2643 individuals;two were at low risk of bias.As no primary outcomes were similar after an identical treatment duration in the included studies,meta-analysis could not be performed.However,more studies favored SFC,instead of MON,owing to a lower risk of asthma exacerbation in the SFC group.As for secondary outcome,SFC showed a significant improvement of peak expiratory flow(PEF)%pred after 4 weeks compared with MFC(mean difference[MD]:5.45;95%confidence interval[CI]:1.57-9.34;I^(2)=95%;P=0.006).As for asthma control level,SFC also showed a higher full-controlled level(risk ratio[RR]:1.51;95%CI:1.24-1.85;I^(2)=0;P<0.001)and higher childhood asthma control test score after 4 weeks of treatment(MD:2.30;95%CI:1.39-3.21;I^(2)=72%;P<0.001)compared with MFC.Conclusions:SFC may be more effective than MFC for the treatment of asthma in children and adolescents,especially in improving asthma control level.However,there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma.Further research is needed,particularly a combination of good-quality long-term prospective studies and well-designed RCTs.PROSPERO registration number:CRD42019133156.展开更多
Salmeterol is a long-acting β2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the imm...Salmeterol is a long-acting β2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells （DCs） are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol （10-s mol/I） reduced the inflammation caused by lipopolysaccharide （0.1 pg/ml） in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B （NF-κB）, mitogen-activated protein kinase （MAPK） pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.展开更多
Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in ...Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting 132-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. Methods An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups （1：1） to receive either the combination of 50 μg salmeterol and 500 μg fluticasone twice daily （n=61）, or the combination of 206 μg albuterol and 36 pg ipratropium q.i.d （n=61） over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. Results Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein （-1.73 vs. 0.08 mg/L, respectively, P 〈0.05） after 6-month treatment. Forced expiratory volume in one second （FEV1） and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV1 and St George＇s Respiratory Questionnaire total scores compared with those who did not （185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P 〈0.01）. Conclusion Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.展开更多
文摘Combined administration of fluticasone propionate and salmeterol xinofoate has been widely used for the treatment of asthma in recent decades. In this investigation, we developed and validated a novel and sensitive ultra performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for simultaneous determination of fluticasone propionate and salmeterol xinofoate in human plasma. Following a simple SPE sample extraction in 96-well plate format, chromatography was performed on a Waters ACQUITY UPLC BEH C 18 column （1.7 μm, 50 min×2.1 mm） with mobile phase consisting of 100% MeOH and 0.1% NH4OH in water on a gradient program at flow rate of 0.5 mL/min. Detection of analytes and internal standards was accomplished using multiple reaction monitoring （MRM） of precursor〉product ion pairs of m/z 501.4〉313.2 （fluticasone propionate）, 506.4〉293.3 （fluticasone propionate-d5）, 416.4〉232.1 （salmeterol xinofoate） and 419.3〉235.2 （salmeterol-d3）. The assay range was 2.50-500 pg/mL for both analytes, and a 1/x2 weighted linear regression model was used. The inter-assay accuracy and precision of the method were within ±8.6%. The recoveries from 0.30 mL of plasma were greater than 51.0% and 54.6% for fluticasone propionate and salmeterol, respectively, and the results were consistent across low, middle and high concentration levels. The method was validated following FDA, EMA and CFDA （China Food and Drug Administration）＇s guidance on bioanalysis and then successfully applied to support a clinical study in healthy Chinese subjects following inhaled administration of a single combination of fluticasone propionate/salmeterol （250 μg/50 μg）.
文摘Background:Despite the recommendation of inhaled corticosteroids(ICSs)plus long-acting beta 2-agonist(LABA)and leukotriene receptor antagonist(LTRA)or ICS/LTRA as stepwise approaches in asthmatic children,there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years.This study aimed to compare the safety and efficacy of salmeterol/fluticasone(SFC)vs.montelukast(MON),or combination of montelukast and fluticasone(MFC)in children and adolescents aged 4 to 18 years with bronchial asthma.Methods:A systematic search was conducted in MEDLINE,EMBASE,the Cochrane Library,China BioMedical Literature Database,Chinese National Knowledge Infrastructure,VIP Database for Chinese Technical Periodical,and Wanfang for randomized controlled trials(RCTs)published from inception to May 24,2021.Interventions are as follows:SFC vs.MON,or combination of MFC,with no limitation of dosage or duration.Primary and secondary outcome measures were as follows:the primary outcome of interest was the risk of asthma exacerbation.Secondary outcomes included risk of hospitalization,pulmonary function,asthma control level,quality of life,and adverse events(AEs).A random-effects(I^(2)≥50%)or fixed-effects model(I^(2)<50%)was used to calculate pooled effect estimates,comparing the outcomes between the intervention and control groups where feasible.Results:Of the 1006 articles identified,21 studies met the inclusion criteria with 2643 individuals;two were at low risk of bias.As no primary outcomes were similar after an identical treatment duration in the included studies,meta-analysis could not be performed.However,more studies favored SFC,instead of MON,owing to a lower risk of asthma exacerbation in the SFC group.As for secondary outcome,SFC showed a significant improvement of peak expiratory flow(PEF)%pred after 4 weeks compared with MFC(mean difference[MD]:5.45;95%confidence interval[CI]:1.57-9.34;I^(2)=95%;P=0.006).As for asthma control level,SFC also showed a higher full-controlled level(risk ratio[RR]:1.51;95%CI:1.24-1.85;I^(2)=0;P<0.001)and higher childhood asthma control test score after 4 weeks of treatment(MD:2.30;95%CI:1.39-3.21;I^(2)=72%;P<0.001)compared with MFC.Conclusions:SFC may be more effective than MFC for the treatment of asthma in children and adolescents,especially in improving asthma control level.However,there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma.Further research is needed,particularly a combination of good-quality long-term prospective studies and well-designed RCTs.PROSPERO registration number:CRD42019133156.
文摘Salmeterol is a long-acting β2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells （DCs） are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol （10-s mol/I） reduced the inflammation caused by lipopolysaccharide （0.1 pg/ml） in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B （NF-κB）, mitogen-activated protein kinase （MAPK） pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.
文摘Background Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting 132-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients. Methods An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups （1：1） to receive either the combination of 50 μg salmeterol and 500 μg fluticasone twice daily （n=61）, or the combination of 206 μg albuterol and 36 pg ipratropium q.i.d （n=61） over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment. Results Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein （-1.73 vs. 0.08 mg/L, respectively, P 〈0.05） after 6-month treatment. Forced expiratory volume in one second （FEV1） and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV1 and St George＇s Respiratory Questionnaire total scores compared with those who did not （185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P 〈0.01）. Conclusion Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.
文摘目的:从中国卫生体系角度出发,评价吸入沙美特罗替卡松(fluticasone propionate/salmeterol,FP/SA)与吸入氟替卡松(fluticasone,FP)治疗哮喘的经济性,为临床用药提供循证治疗依据。方法:基于一项国际多中心随机对照临床研究(AUSTRI研究)建立哮喘Markov模型,模拟FP/SA组和FP组治疗哮喘无急性发作、急性发作及死亡的动态变化,模拟时限为10年,循环周期为1个月。成本仅纳入直接医疗成本,药品单价来源于药智网最新数据,效用值和住院成本来源于文献数据。以2023年3倍国内生产总值(GDP)作为意愿支付(willingness-to-pay,WTP)阈值,应用TreeAge Pro 2011软件进行回乘分析和队列模拟,同时采用敏感性分析评价基础研究结果的稳健性。结果:吸入沙美特罗替卡松与吸入氟替卡松治疗方案的总成本分别为3805.87、3244.64元,效用值分别为11.7056、11.5635 QALYs,FP/SA组相对于FP组的ICER为3949.54元/QALY,小于WTP阈值(268200元/QALY)。单因素敏感性分析结果显示,FP/SA组和FP组药品成本是主要影响参数,但对基础分析结果影响不大。概率敏感性分析结果显示,FP/SA组具有经济性的概率为90.5%。结论:与氟替卡松治疗方案相比,规律吸入沙美特罗替卡松对于哮喘患者来说更具有经济性。
