丙酸氟替卡松联合布地奈德治疗小儿支气管哮喘的临床研究

目的探讨丙酸氟替卡松吸入气雾剂联合吸入用布地奈德混悬液治疗小儿支气管哮喘的临床疗效。方法选取2015年1月—2016年1月在第四军医大学第一附属医院治疗的支气管哮喘患儿96例作为研究对象,利用随机数字表法将患儿分为对照组和治疗组,每组各48例。对照组雾化吸入吸入用布地奈德混悬液,0.5 mg/次,2次/d。治疗组在对照组基础上吸入丙酸氟替卡松吸入气雾剂,2揿/次,2次/d。两组患儿均连续治疗12周。观察两组的临床疗效,比较两组肺功能、血气指标和炎性因子情况。结果治疗后,对照组和治疗组总有效率分别为83.3%、95.8%,两组比较差异有统计学意义(P0.05)。治疗后,两组呼气峰流速值(PEF)、1 s用力呼气容积(FEV1)、呼气高峰流量(PEFR)和FEV_1/用力肺活量(FVC)均明显上升,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血氧分压(Pa O_2)和酸碱度(p H)值均显著上升,二氧化碳分压(Pa CO2)均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP)、白细胞介素4(IL-4)、白细胞介素8(IL-8)和白细胞介素13(IL-13)水平均明显下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论丙酸氟替卡松吸入气雾剂联合吸入用布地奈德混悬液治疗小儿支气管哮喘具有较好的疗效,可改善肺功能,缓解炎症反应,具有一定临床推广应用价值。     

2011-2015年南京市第一医院肺部吸入制剂的使用情况分析

目的 分析南京市第一医院肺部吸入制剂的使用情况,为临床合理使用提供参考.方法 对2011—2015年南京市第一医院肺部吸入制剂的种类、用药金额、用药频度(DDDs)、日均药费(DDC)及药品排序比(B/A)等进行统计和分析.结果 2011—2015年肺部吸入制剂的用药金额均呈上升趋势,但占总用药金额的构成比基本稳定.其中用药金额前3位的肺部吸入制剂为吸入用布地奈德混悬液、沙美特罗替卡松粉吸入剂、布地奈德福莫特罗粉吸入剂;DDDs排名前3位的肺部吸入制剂分别为沙美特罗替卡松吸入剂、吸入用布地奈德混悬液、沙丁胺醇气雾剂;沙丁胺醇气雾剂、沙美特罗替卡松吸入剂、噻托溴铵粉吸入剂的B/A较大,而吸入用异丙托溴铵溶液、吸入用布地奈德混悬液的B/A较小,其余吸入制剂的B/A基本接近1.00.DDC排名前3位的肺部吸入制剂分别为吸入用布地奈德混悬液、吸入用异丙托溴铵溶液、布地奈德福莫特罗粉吸入剂.结论 2011—2015年南京市第一医院肺部吸入制剂总体用药和价格结构比较客观合理.     

10S精益管理提升静脉用药调配中心服务质量的实践与应用

目的：分析儿科住院患者吸入用布地奈德混悬液的使用情况,为临床合理用药提供参考。方法：采用回顾性调查方法,从2018年5月至2019年4月儿科住院患者吸入用布地奈德混悬液使用率前10位科室中,每个科室随机抽取30份病历,共计300份,对吸入用布地奈德混悬液使用情况进行统计和分析。结果：107例（35.6%）适应证不合理,148例（49.3%）用药频次不合理,231例（77.0%）雾化时合并使用了其他药物,4例发生不良反应。结论：医院应加强超说明书用药的监管,制定吸入用布地奈德混悬液合理用药标准,提高合理用药水平。     

特殊制剂体外群体生物等效性研究案例分析

目的：采用体外群体生物等效性评价方法评估4种特殊制剂的等效性。方法：对国内外指南中关于群体生物等效性的内容进行总结,选择混合标度法,针对不同制剂,主要考察粒径参数、给药装置等体外测量数据参数,将指南中的公式和方程运用于2种吸入制剂（吸入用布地奈德混悬液和左沙丁胺醇雾化吸入溶液）以及2种脂质纳米注射剂（阿扎胞苷注射剂和注射用白蛋白结合型紫杉醇）的等效性研究。结果：该文的体外群体生物等效性研究取得良好的实践结果,除了阿扎胞苷注射剂的受试制剂与参比制剂不等效,需要对粒径继续加以改进外,其他3种制剂有95%的把握度说明受试制剂与参比制剂等效。结论：该研究成功将指南中的公式运用在实际案例中,对特殊制剂体外群体生物等效性在制剂研发中的应用有指导意义。     

布地奈德混悬液雾化吸入治疗儿童哮喘的疗效观察

目的观察布地奈德混悬液雾化吸入治疗儿童哮喘的疗效。方法将随机抽样62例分为两组,符合支气管哮喘诊断标准的儿童均给予一般治疗,如镇静,吸氧及加用β2-受体激动剂雾化吸入等治疗,治疗组患儿加用布地奈德溶液雾化吸入治疗。结果治疗组总有效率93.75%,对照组总有效率76.67%。结论用布地奈德混悬液雾化吸入治疗儿童哮喘,对改善症状和缩短病程有显著疗效。     

布地奈德混悬液雾化吸入治疗小儿急性喉炎的疗效观察

目的研究布地奈德混悬液雾化吸入治疗小儿急性喉炎的疗效。方法选择67例急性喉炎患儿,随机分为治疗组与对照组。治疗组加用布地奈德混悬液雾化吸入,对照组采用地塞米松静脉给药,比较两组患儿的疗效。结果两组疗效比较,存在显著性差异（P〈0．005）。结论布地奈德混悬液雾化吸入治疗小儿急性喉炎起效快,疗效好,不良反应少。     

布地奈德混悬液联合复方异丙托溴铵溶液雾化吸入治疗毛细支气管炎的效果分析

目的探讨吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液佐治毛细支气管炎的临床效果。方法将78例毛细支气管炎患儿随机分为两组,对照组采用止咳祛痰、平喘、吸氧、镇静及抗病毒等常规治疗,观察组在对照组基础上,采用吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液治疗。比较两组的疗效、喘憋缓解时间、喘鸣音消失时间和肺部湿啰音消失时间。结果观察组的总有效率为82.5%,高于对照组的57.9%,差异有统计学意义（P〈0.05）。两组的喘憋缓解时间、喘鸣音消失时间和肺部湿啰音消失时间比较差异有统计学意义（P〈0.05）。两组用药后均无严重副反应。结论吸入用布地奈德混悬液联合吸入用复方异丙托溴铵溶液治疗毛细支气管炎的效果明显。     

硫酸特布他林雾化溶液及吸入用布地奈德混悬液联合吸入治疗小儿毛细支气管炎的疗效观察

目的 观察硫酸特布他林雾化溶液及吸入用布地奈德混悬液联合吸入治疗小儿毛细支气管炎的疗效.方法 选择100例门诊确诊为小儿毛细支气管炎的患者,并随机分为两组,观察组60例和对照组40例.两组患儿均采用综合性治疗,包括抗生素、抗病毒、止咳对症等治疗,观察组在此综合治疗基础上加用硫酸特布他林雾化溶液及吸入用布地奈德混悬液氧气驱动雾化吸入治疗.用法为每次两种药物各1mL（分别含特布他林2.5mg和布地奈德0.5mg）由空气压缩泵雾化吸入.每天2次,每次8～10min.疗程为5d.结果 观察组总有效率为100%,对照组总有效率为80%.结论 硫酸特布他林雾化溶液及吸入用布地奈德混悬液氧气驱动联合雾化吸入治疗小儿毛细支气管炎疗效显著,方便安全,值得推广.     

布地奈德联合硫酸沙丁胺醇治疗儿童咳嗽变异型哮喘140例观察

目的探讨吸入用布地奈德混悬液联合吸入用硫酸沙丁胺醇溶液治疗儿童咳嗽变异型哮喘的疗效。方法全部患者均来自我院,符合儿童哮喘防治常规(试行)[1],随机分为两组,A组:吸入用布地奈德混悬液联合吸入用硫酸沙丁胺醇溶液。B组:单用吸入用布地奈德混悬液。每个患儿在用药前及用药期间,每天早晨起床后和晚临睡前用峰速仪测最大呼吸流量PEF,PEFR并观察记录临床症状和体征以及合理用药或不良反应。结果治疗后A、B两组患儿临床症状和体征均有好转,A、B间无明显差异(P>0.05),且治疗期间早晚PEF值测定均有不同程度的增加,日PEF变异率趋向缩小,A组比B组更明显(P<0.05),具有统计学意义。结论应用吸入用布地奈德混悬液联合吸入用硫酸沙丁胺醇溶液治疗儿童咳嗽变异型哮喘与对照组吸入用布地奈德混悬液疗效相似,副作用少,且日PEF变异率缩小程度优于对照组,是治疗儿童咳嗽变异型哮喘较好的治疗方案,值得临床推荐应用。     

吸入用布地奈德混悬液联合复方异丙托溴铵气雾剂雾化吸入治疗慢性阻塞性肺疾病急性加重疗效的Meta分析

目的 系统评价吸入用布地奈德混悬液联合复方异丙托溴铵气雾剂雾化吸入治疗慢性阻塞性肺疾病急性加重（AECOPD）的疗效.方法 计算机检索PubMed、西文生物医学期刊文献数据库、中国期刊全文数据库（CNKI）、中国科技期刊数据库（VIP）、中国医院知识总库（CHKD）及万方数据等数据库,纳入所有吸入用布地奈德混悬液联合复方异丙托溴铵气雾剂雾化吸入治疗AECOPD疗效的随机对照试验.按纳入与排除标准筛选文献、评价质量和提取有效数据后,采用RevMan5.2软件进行Meta分析.结果 最终纳入8个随机对照试验,共638例患者.Meta分析结果显示：与对照组比较,吸入用布地奈德混悬液联合复方异丙托溴铵气雾剂雾化吸入明显改善AECOPD患者动脉血氧分压[均数差（MD）=5.50,95％置信区间（CI）：1.06～9.95,Z=2.43,P=0.02]和第1秒钟用力呼气容积占预计值的百分比（FEV1％）[MD=6.02,95％ CI：2.29 ～9.04,Z=3.90,P＜0.01],差异有统计学意义;其治疗AECOPD的总有效率高于对照组,差异有统计学意义[相对危险度（RR）=4.90,95％ CI：2.45～9.78）,Z=4.50,P＜0.01].结论 吸入用布地奈德混悬液联合复方异丙托溴铵气雾剂雾化吸入能有效改善AECOPD患者肺通气功能,纠正低氧,改善临床症状.     

沙美特罗替卡松粉吸入剂治疗哮喘的临床疗效分析

目的：观察吸入沙美特罗替卡松粉治疗成人哮喘的临床疗效。方法：将80例哮喘患者分为治疗组与对照组,治疗组给予沙美特罗替卡松粉吸入治疗,对照组给予布地奈德粉吸入剂治疗。观察患者治疗前后临床症状及肺功能[用力呼气肺活量（FVC）,第1秒用力呼气容积率（FEV1%）和用力呼气峰流速（PEFR）]的变化。结果：与治疗前比较,两组患者治疗后临床症状、肺功能各项指标、血清IL-4和IgE水平均得到明显改善;治疗后治疗组临床疗效、肺功能FVC、FEV1%和PEFR均明显优于对照组,但两者血清IL-4和IgE水平差异无统计学意义。结论：沙美特罗替卡松粉吸入剂治疗成人哮喘疗效显著,适于临床应用。     

Treatment of childhood asthma: how do the available options compare?

The National Asthma Council of Australia suggests that "the aim of preventive therapy should be to enable patients to enjoy a normal life (comparable with that of non-asthmatic children), with the least amount of medication and at minimal risk of adverse events. The level of maintenance therapy should be determined by symptom control and lung function in the interval periods." The British Thoracic Society/Scottish Intercollegiate Guidelines Network states that the aims of the pharmacological treatment of asthma should be to control symptoms, prevent exacerbations and achieve the best possible lung function with minimal adverse effects. We have used the current published international guidelines to highlight the international differences in management recommendations, and compared the possible pharmacological options with a focus on the above ideals. Cromones have been used for many years in childhood asthma. Most evidence suggests they now have little role. Regarding inhaled corticosteroids (ICS), beclomethasone and budesonide are essentially similar in their efficacy. Fluticasone propionate is equally as effective at one-half the equivalent dose of budesonide or beclomethasone. Adverse effects are rare in dosages <400 microg/day of budesonide and beclomethasone or <200 microg/day of fluticasone propionate, but may occur in individual patients. Relevant clinical adverse effects are rare and pharmacological systemic effects are less noticeable with budesonide and fluticasone propionate than with beclomethasone, but data are conflicting. Long-acting beta2-adrenoceptor agonists (beta2-agonists) are recommended once low-dose ICS have failed to control symptoms. The main pharmacological difference between the agents is that formoterol is a full beta2-adrenergic agonist, whereas salmeterol is a partial agonist at the beta2-adrenoceptor and has a unique pharmacological action. The main clinical distinction between these two agents is that their onset of bronchodilation differs. Bronchodilation begins at about 3 minutes after inhalation of formoterol, which is similar to the short-acting agents, whereas salmeterol has a much slower onset of action at about 15-30 minutes. The many in vitro differences between the two drugs are probably not clinically relevant. There are no comparative pediatric data on the leukotriene modifiers to make clear recommendations.     

沙美特罗替卡松粉吸入剂中沙美特罗和丙酸氟替卡松的HPLC测定

建立了HPLC法测定沙美特罗替卡松粉吸入剂中的沙美特罗和丙酸氟替卡松.采用C_(18)色谱柱,以甲醇-0.05 mol/L乙酸铵溶液(68:32)为流动相,检测波长228 nm.沙美特罗和丙酸氟替卡松分别在0.14～27.4 μg/ml和0.3～60μg/ml浓度范围内线性关系良好;回收率为101.3%和101.5%.     

Evidence of the in vivo esterification of budesonide in human airways

AIMS

Budesonide, unlike fluticasone propionate, undergoes fatty acid esterification in the lungs, and there is a need to characterize fully the distribution and fate of the two drugs after inhalation in humans.

METHODS

This open-label, randomized study was performed in adults undergoing whole lung or lobar resection resulting from lung cancer. Patients were given single 1000-μg doses of both budesonide and fluticasone propionate via dry powder inhalers before surgery. Tissue samples from peripheral and central lung, an ex vivo bronchial brush sample and intercostal muscle, together with plasma samples, were taken during surgery and analysed by liquid chromatography plus tandem mass spectrometry.

RESULTS

Lung tissue samples were obtained from 22 patients at surgery, 1–43 h after drug dosing. Budesonide was detectable from earliest sampling in central and peripheral lung tissue up to 10 h (in six of 22 samples), fluticasone propionate up to 22 h after inhalation (in 16 of 22 samples), and budesonide oleate up to 43 h after inhalation (in 21 of 22 samples). Budesonide, but not fluticasone propionate, was detected in intercostal muscle for up to 10 h after inhalation. Bronchial brush samples showed the presence of fluticasone propionate for up to 18 h, suggesting the presence of undissolved drug powder particles in the airway lumen.

CONCLUSION

Sustained retention of esterified budesonide in the lungs supports the prolonged duration of action of budesonide and suitability for once-daily administration.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• In vitro studies with human bronchial epithelial cells have shown that budesonide undergoes rapid, extensive and reversible intracellular esterification, a finding that is believed to contribute to retention and prolonged duration of action.
• A case report has suggested retention of budesonide in the lungs of patients undergoing surgical resection.
• This study evaluated, for the first time, the esterification (and distribution) of inhaled budesonide and fluticasone propionate in vivo in human lung.

WHAT THIS STUDY ADDS

• This study has unequivocally shown that budesonide undergoes esterification in human lungs in vivo.
• Budesonide was detectable in central and peripheral lung tissue for 10 h, and budesonide oleate up to 43 h after inhalation.
• The sustained retention of budesonide esters in the lungs probably contributes to the prolonged duration of action and once-daily efficacy of budesonide.

     

我院2008—2010年哮喘类疾病用药消耗分析

目的了解我院哮喘类疾病临床用药情况及发展趋势,为临床合理用药提供参考。方法采用医院药库2008—2010年哮喘病治疗主要用药出库数据,从购药金额、用药频度（DD慨）等方面进行统计、分析用药特点。结果我院2008—2010年3年来哮喘类疾病购药金额和使用量呈上升趋势;购药金额按用药途径排名,第1位是吸入剂类哮喘用药;购药金额按种类排名,第1位是肾上腺皮质激素类药物;购药金额单项前3位药品为布地奈德混悬剂、沙美特罗替卡松吸入剂、盂鲁司特钠片剂;DDDs排名前3位药品为沙丁胺醇雾化溶液、沙美特罗替卡松吸入剂、孟鲁司特钠片剂。结论我院临床在哮喘类疾病用药方面基本符合支气管哮喘防治指南用药规范,总体用药种类及价格结构比较客观合理。     

沙美特罗氟替卡松联合孟鲁司特钠治疗慢性支气管炎临床观察

目的：对在慢性支气管炎治疗中,运用沙美特罗氟替卡松粉吸入剂与孟鲁司特钠的效果进行观察。方法：通过随机对照研究,对比观察组采用沙美特罗氟替卡松联合孟鲁司特钠治疗,对照组采用沙美特罗氟替卡松治疗的临床效果及肺功能改善情况。结果：观察组总有效率为92.59%,对照组总有效率为70.37%;观察组肺功能各项指标改善效果更加显著。结论：在慢性支气管炎治疗中,采用沙美特罗氟替卡松粉吸入剂与孟鲁司特钠进行联合治疗效果显著。     

某三级甲等医院住院患者雾化吸入用药分析

目的:了解某三级甲等医院(以下简称“该院”)住院患者雾化吸入用药使用情况,为临床合理用药提供参考。方法:利用医院信息系统,抽取2019年1—6月该院住院患者给药途径为雾化吸入的长期医嘱12075条,收集科室、患者基本信息、药品名称、用法、用量和临床诊断等信息,对限定日剂量、处方日剂量和药物利用指数(drug utilization index,DUI)等进行统计分析。结果:12075条雾化吸入用药医嘱涉及住院患者3209例,年龄1 d至98岁,≥60岁患者医嘱数居多,共5744条(占47.57%);涉及31个临床科室,主要为脊柱外科、呼吸科和耳鼻喉科;疾病诊断以呼吸系统疾病为主;涉及药品21个品规,使用例次数排序居前3位的为吸入用布地奈德混悬液、吸入用乙酰半胱氨酸溶液和盐酸氨溴索注射液;雾化制剂的医嘱数为5443条,涉及6个品规,仅吸入用乙酰半胱氨酸溶液的DUI>1,提示该药处方日剂量超过药品说明书规定的最大日剂量;非雾化制剂用于雾化途径属于超说明书用药,医嘱数为6632条;涉及2077组联合用药,二联用药主要为吸入用布地奈德混悬液+吸入用乙酰半胱氨酸溶液、吸入用布地奈德混悬液+吸入用硫酸沙丁胺醇溶液或硫酸特布他林雾化液、吸入用布地奈德混悬液+吸入用异丙托溴铵溶以及吸入用布地奈德混悬液+盐酸氨溴索注射液或注射用盐酸氨溴索等,三联用药主要为吸入用布地奈德混悬液+吸入用硫酸沙丁胺醇溶液或硫酸特布他林雾化液+吸入用异丙托溴铵溶,还存在四联用药情况;单次给药量范围为2~110 ml,平均给药量(9.52±5.76)ml。结论:雾化吸入治疗临床应用广泛,但雾化制剂品种选择较少,临床使用存在单次给药剂量不准确、联合用药不合理及非雾化制剂滥用等情况,需加强监管,促进雾化用药的合理应用。     

Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review of its use in the management of asthma

Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone propionate alone. The combination product also appears to improve HR-QOL relative to placebo or salmeterol alone.