The apparent degradation rate constant of fluticasone propionate(FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169 ± 0.003 h^(-1), and four degradation products(products 1–4) were...The apparent degradation rate constant of fluticasone propionate(FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169 ± 0.003 h^(-1), and four degradation products(products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH_3CN=1:1 were 0.472 ± 0.013 h^(-1) and 0.154 ± 0.000 h^(-1)(n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance(NMR)and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH_3CN=1:1 was found to be product 2 based on ~1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.展开更多
Lichen planus is a fairly common chronic idiopathic disorder of the skin,nails and mucosal surfaces.Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in litera...Lichen planus is a fairly common chronic idiopathic disorder of the skin,nails and mucosal surfaces.Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature.Given its rarity,it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis.Currently,there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach.Systemic steroids are usually the first line treatment and offer a favorable response.In this report,we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk,as evidenced by objective clinical findings.Based on our review of related literature and experience in this patient,we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment.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
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
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
Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,...Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,these localized forms of steroid therapy are generally considered to have fewer systemic side effects compared to long-term oral corticosteroids.However,concern and controversy remain over the impact of ICS and INS on the incidence and control of diabetes mellitus(DM).Given the widespread use of ICS and INS,even small individual effects on DM could lead to large consequences for the global population.Multiple large observational studies suggest that high dose ICS is associated with increased incident DM and worsened DM control,though the contribution of other risk factors is less certain.In addition,only two studies were done to investigate the association of INS and DM,with both studies demonstrating a short-term association of INS use with hyperglycemia.While more research evaluating the risk of ICS/INS for DM-related adverse events is needed,high doses of ICS/INS should be avoided when possible.The following strategies for ICS/INS dose minimization can be considered:Use of non-pharmacological measures(trigger avoidance,smoking cessation,vaccination to avoid infection),control of comorbid conditions,use of non-ICS-containing medications,intermittent rather than regular ICS dosing,and appropriate de-escalation of high ICS doses.展开更多
Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a firs...Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.展开更多
Background:Chronic obstructive pulmonary disease(COPD)is a more prevalent chronic lung disease with a significant health burden,and the majority of these cases receive inadequate treatment.Methods:Prospective,observat...Background:Chronic obstructive pulmonary disease(COPD)is a more prevalent chronic lung disease with a significant health burden,and the majority of these cases receive inadequate treatment.Methods:Prospective,observational,interview(questionnaire)based complete workup COPD study,screened 12,000 cases with chronic respiratory symptoms with cough,sputum production,and shortness of breath.A total of 6000 COPD cases were enrolled after the spirometry test.COPD cases were assessed as disease knowledge and methods of treatment offered by applying questionnaires to patients and treating physicians.Results:In the present study,3%of study cases were aware of their COPD illness,54%were not having knowledge about the disease,and 43%cases were not accepting the COPD diagnosis(p<0.0001).A total of 58%of cases received inhalation treatment as levosalbutamol monotherapy in 31%cases,levosalbutamol plus beclometasone in 18%cases,and formoterol plus budesonide or salmeterol plus fluticasone only in 9%of COPD cases(p<0.0001).Total 42%cases received oral treatment as theophylline in 16%cases,salbutamol in 7%cases,oral steroids in 19%cases(p<0.0001).Conclusion:"Doctor–patient–drug trio"discordance clubbed as"difficult doctor,difficult patient,and difficult treatment"is a very crucial issue observed during diagnosis and management of COPD in peripheral settings in India.展开更多
文摘The apparent degradation rate constant of fluticasone propionate(FLT) in 0.1 M NaOH:methanol=1:1 at 37 °C was previously reported to be 0.169 ± 0.003 h^(-1), and four degradation products(products 1–4) were observed in the solution. The aims of the present study were to assess the degradation rates of FLT in other alkaline solutions and clarify the chemical structures of the four degradation products in order to obtain basic data for designing an enema for inflammatory bowel disease. The apparent degradation rate constants in 0.05 M NaOH and 0.1 M NaOH:CH_3CN=1:1 were 0.472 ± 0.013 h^(-1) and 0.154 ± 0.000 h^(-1)(n=3), respectively. The chemical structures of products 1–4 in 0.1 M NaOH:methanol=1:1 were revealed by nuclear magnetic resonance(NMR)and mass spectrometry data. The chemical structure of products 2 was that the 17-position of the thioester moiety of FLT was substituted by a carboxylic acid. The degradation product in 0.1 M NaOH:CH_3CN=1:1 was found to be product 2 based on ~1H NMR data. The degradation product in 0.05 M NaOH was considered to be product 2 based on the retention time of HPLC. These results are useful for detecting the degradation products of FLT by enzymes of the intestinal bacterial flora in the large intestine after dosing FLT as an enema.
文摘Lichen planus is a fairly common chronic idiopathic disorder of the skin,nails and mucosal surfaces.Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature.Given its rarity,it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis.Currently,there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach.Systemic steroids are usually the first line treatment and offer a favorable response.In this report,we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk,as evidenced by objective clinical findings.Based on our review of related literature and experience in this patient,we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment.
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Inhaled corticosteroids(ICS)and intranasal corticosteroids(INS)are the mainstays of treatment for chronic respiratory diseases like asthma,chronic obstructive pulmonary disease,and allergic rhinosinusitis.In addition,these localized forms of steroid therapy are generally considered to have fewer systemic side effects compared to long-term oral corticosteroids.However,concern and controversy remain over the impact of ICS and INS on the incidence and control of diabetes mellitus(DM).Given the widespread use of ICS and INS,even small individual effects on DM could lead to large consequences for the global population.Multiple large observational studies suggest that high dose ICS is associated with increased incident DM and worsened DM control,though the contribution of other risk factors is less certain.In addition,only two studies were done to investigate the association of INS and DM,with both studies demonstrating a short-term association of INS use with hyperglycemia.While more research evaluating the risk of ICS/INS for DM-related adverse events is needed,high doses of ICS/INS should be avoided when possible.The following strategies for ICS/INS dose minimization can be considered:Use of non-pharmacological measures(trigger avoidance,smoking cessation,vaccination to avoid infection),control of comorbid conditions,use of non-ICS-containing medications,intermittent rather than regular ICS dosing,and appropriate de-escalation of high ICS doses.
文摘Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.
文摘Background:Chronic obstructive pulmonary disease(COPD)is a more prevalent chronic lung disease with a significant health burden,and the majority of these cases receive inadequate treatment.Methods:Prospective,observational,interview(questionnaire)based complete workup COPD study,screened 12,000 cases with chronic respiratory symptoms with cough,sputum production,and shortness of breath.A total of 6000 COPD cases were enrolled after the spirometry test.COPD cases were assessed as disease knowledge and methods of treatment offered by applying questionnaires to patients and treating physicians.Results:In the present study,3%of study cases were aware of their COPD illness,54%were not having knowledge about the disease,and 43%cases were not accepting the COPD diagnosis(p<0.0001).A total of 58%of cases received inhalation treatment as levosalbutamol monotherapy in 31%cases,levosalbutamol plus beclometasone in 18%cases,and formoterol plus budesonide or salmeterol plus fluticasone only in 9%of COPD cases(p<0.0001).Total 42%cases received oral treatment as theophylline in 16%cases,salbutamol in 7%cases,oral steroids in 19%cases(p<0.0001).Conclusion:"Doctor–patient–drug trio"discordance clubbed as"difficult doctor,difficult patient,and difficult treatment"is a very crucial issue observed during diagnosis and management of COPD in peripheral settings in India.
