Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal sprays

Objectives To compare the systemic exposure for intranasal mometasone furoate (MF) and fluticasone propionate (FP) aqueous nasal sprays (ANS) in terms of serum and urinary cortisol parameters and plasma pharmacokinetics.Methods Twelve healthy subjects completed this three-way, cross-over study. They received FPANS (50 g/spray), MFANS (50 g/spray) or placebo ANS, eight sprays per nostril every 8 h for 4 days. Cortisol measurements were made at baseline and day 4. FP and MF plasma concentrations were also measured on day 4.Results MFANS produced similar mean plasma AUC (123 pmol/l h) to FPANS (112 pmol/l h). Despite the use of high doses, necessary to generate adequate pharmacokinetic data, only minor reductions in cortisol parameters were found, with no difference between FPANS and MFANS.Conclusions FP and MF have similar and very low systemic bioavailability when administered intranasally using a high-dose regimen. It is therefore unlikely that therapeutic doses of intranasal FP or MF will produce dissimilar or significant degrees of systemic exposure or systemic effects.     

Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration

Objective: To evaluate the pharmacokinetic and systemic pharmacodynamic properties of inhaled fluticasone propionate (FP). Methods: Single doses of 0.25, 0.5, 1.0 and 3.0 mg FP were administered to groups of six healthy subjects. Serum concentration profiles of FP were monitored over 24 h by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS–MS). Systemic pharmacodynamic effects were evaluated by measuring endogenous serum cortisol and circulating white blood cells, and analyzed with previously developed integrated pharmacokinetic/pharmacodynamic (PK/PD) models. Results: FP showed a dose-independent terminal half-life with a mean (SD) of 6.0 (0.7) h. Maximum serum concentrations occurred 1.0 (0.5) h after administration, ranging from 90 pg · ml⁻¹ for the 0.25 mg dose to 400 pg · ml⁻¹ for the 3.0 mg dose. This, together with an estimated mean absorption time of nearly 5 h and a known oral bioavailability of less than 1%, indicates prolonged residence at and slow absorption from the lungs. In the investigated dose range, the cumulative systemic effect was dose-dependent for both markers of pharmacodynamic activity. For doses of 0.25, 0.50, 1.0 and 3.0 mg FP, the PK/PD-based cumulative systemic-effect parameters were 159, 186, 257 and 372% · h for lymphocyte suppression, 107, 186, 202 and 348% · h for granulocyte induction and 23.6%, 33.8%, 51.0% and 73.6% for cortisol reduction, respectively. The time courses of lymphocytes, granulocytes and endogenous cortisol could be sufficiently characterized with the applied PK/PD models. The measured in vivo EC₅₀ values, 30 pg · ml⁻¹ and 7.3 pg · ml⁻¹ for white blood cells and cortisol, respectively, were in good agreement with predictions based on the in vitro relative receptor affinity of FP. Conclusion: After inhalation, FP follows linear pharmacokinetics and exhibits dose-dependent systemic pharmacodynamic effects that can be described by PK/PD modeling. Received: 27 January 1997 / Accepted in revised form: 5 August 1997     

沙美特罗/丙酸氟替卡松联合异丙托溴铵吸入治疗重度COPD的临床研究

目的：研究沙美特罗/丙酸氟替卡松联合异丙托溴铵吸入治疗重度慢性阻塞性肺疾病（COPD）稳定期患者的临床疗效。方法：随机抽取80例COPD患者分为观察组和对照组,观察组给予沙美特罗/丙酸氟替卡松合并异丙托溴铵吸入治疗,对照组给予沙美特罗/丙酸氟替卡松治疗。分别对两组患者治疗前后的情况进行比较。结果：两组治疗后SGRQ积分均较治疗前有明显下降,但观察组下降更明显。两组治疗后的肺功能、血气等指标均有不同程度的改善,但观察组肺功能指标优于对照组。结论：联合用药治疗COPD稳定期患者具有较好的疗效,能够明显地改善COPD患者的血气和肺功能,良好地控制COPD的发展。     

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects

Aims The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of fluticasone propionate (FP) can be explained by systemic accumulation.
Methods Twelve healthy subjects (six women) were given, in a crossover fashion, a single dose inhalation (1000  &;mgr;g) of FP via Diskhaler and repeated inhalations (1000  &;mgr;g twice daily) every 12  h during 7 days. There was a washout period of 2 weeks between the treatments. An intravenous dose of 20  μg FP was given as a reference. Plasma concentrations of FP for each treatment were determined by liquid chromatography plus tandem mass spectrometry. Plasma cortisol after the inhaled doses was determined using an immunoassay and was compared with baseline values.
Results The average plasma concentration of FP was about 1.7 times higher after multiple inhalations than after a single dose. Systemic availability, mainly attributable to pulmonary deposition, was 15.6 [13.6–18.0]% of the nominal dose. Daytime plasma cortisol suppression vs baseline was 47 [20–65]% and 95 [93–97]% for the single and repeated doses, respectively.
Conclusions To conclude, a slow elimination of FP leads to accumulation during repeated dosing. This accumulation may explain the marked decrease in plasma cortisol seen during treatment with fluticasone propionate within the clinical dose range.     

Formulation of novel dry powder inhalation for fluticasone propionate and salmeterol xinafoate with capsule-based device

The aim of this study was to develop a novel fluticasone propionate (FP) and salmeterol xinafoate (SX)-loaded dry powder inhaler (DPI) system, which was composed of powder formulation and performance. The air flow resistances were determined with various types of DPI device, showing that the modified RS01 device gave the specific resistance similar to the commercial DPI device. The particle properties of FP, SX, and inhalation grade lactose particles, such as particle size, size distribution, and fine content, were assessed. Subsequently, the aerodynamic behaviors of the DPI powder formulations were evaluated by the in vitro deposition of drugs in the DPI products using Andersen cascade impactor. Amongst the DPI powder formulations tested, the formulation composed of FP, SX, Respitose^® SV003, Respitose^® SV010, and Respitose^® ML006 at the weight ratio of 0.5/0.145/19/19/2 gave depositions, emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter of drugs similar to the commercial product, suggesting that they had similar aerodynamic behaviors. Furthermore, it gave excellent content uniformity. Thus, this DPI using the modified RS01 device would be recommended as a candidate for FP and SX-loaded pharmaceutical DPI products.     

沙美特罗替卡松吸入治疗儿童哮喘的疗效观察及护理

目的:观察沙美特罗替卡松吸入治疗儿童哮喘的疗效和护理方法。方法:按病情轻、中、重度持续不同,分别给予不同剂量沙美特罗替卡松吸入,同时按需使用短效β2受体激动剂吸入,对<7岁的患儿可加用储雾罐。并由专科护士讲解使用方法。结果:治疗2周后,日间、夜间症状、肺部哮鸣音评分显著下降,治疗至6个月时无症状的病例已达99.15%,治疗2周后用万托林的量明显减少。6月时有记录的357例随访中显效355例(99.4%),有效1例(0.3%),无效1例(0.3%),总有效率99.7%。结论:沙美特罗替卡松治疗哮喘,只要用量恰当,吸入的方法正确,可以减少哮喘发作的次数和减轻哮喘发作的程度。     

Detection of fluticasone propionate in horse plasma and urine following inhaled administration

Fluticasone propionate (FP) is an anti‐inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid‐dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP‐17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC‐MS/MS) in order to detect the extremely low concentrations of analyte present in both matrices. The developed methods were used to analyse plasma and urine samples collected following inhaled administration of FP to six thoroughbred horses. FP was detected in plasma for a minimum of 72 h post‐administration and FP‐17βCOOH was detected in urine for approximately 18 h post‐administration. The results show that it is possible to detect FP in the horse following inhaled administration. Copyright © 2012 John Wiley & Sons, Ltd.     

沙美特罗替卡松治疗慢性阻塞性肺疾病急性加重期临床研究

目的探讨沙美特罗替卡松治疗慢性阻塞性肺疾病急性加重期疗效。方法将笔者所在医院2012年1月～2012年4月收治的COPD急性加重期患者分为实验组和对照组,对照组患者给予一般治疗,实验组患者在对照组基础上加用沙美特罗替卡松治疗,观察两组患者临床症状改善情况以及SGRQ评分。结果实验组治疗后其喘息、咳嗽、哮鸣音等临床症状改善情况均明显优于对照组(P<0.05),治疗后SGRQ评分明显优于对照组,差异有统计学意义(P<0.05)。结论沙美特罗替卡松对慢性阻塞性肺疾病急性加重期安全有效,可显著改善患者肺功能,值得在临床工作中推广应用。     

Mometasone furoate vs fluticasone propionate with salmeterol: multivariate analysis of resource use and asthma-related charges

Abstract

Objective:

Although current National Asthma Education and Prevention Program (NAEPP) guidelines indicate low-dose inhaled corticosteroid (ICS) monotherapy as the preferred treatment for patients with mild persistent asthma, many patients receive ICS and long-acting β₂-agonist (LABA) combinations. The objective of the current study was to evaluate asthma-related charges in patients with mild asthma who began treatment with mometasone furoate (MF) versus those who began treatment with a fluticasone propionate/salmeterol (FPS) combination.     

沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病的疗效观察

目的 观察沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)的临床疗效.方法 108例COPD患者,随机分为实验组和对照组,各54例.对照组予口服盐酸氨溴索片、茶碱缓释片等进行常规治疗,实验组在常规治疗的基础上同时给予沙美特罗替卡松粉吸入治疗.比较两组患者治疗前后的肺功能指标[第1秒用力呼气容积(FEV1)、第1秒...     

联合应用沙美特罗替卡松与噻托溴铵对慢性阻塞性肺疾病肺功能的疗效

目的：联合应用沙美特罗替卡松与噻托溴铵治疗慢性阻塞性肺疾病（COPD）,并观察其疗效。方法：将88例中重度COPD患者随机分为3组,联合治疗组给予吸入沙美特罗替卡松50/500μg,每日2次与噻托溴铵干粉剂18μg,每日1次;噻托溴铵组给予吸入噻托溴铵干粉剂18μg,每日1次;沙美特罗替卡松组给予吸入沙美特罗替卡松50/500μg,每日2次,在治疗前及治疗后测定肺功能。结果：与同组治疗前相比,治疗后噻托溴铵组、沙美特罗替卡松组、联合治疗组第1秒用力呼气量（FEV1）显著提高（P〈0.05）,第1秒用力呼气容积/用力肺活量、第1秒用力呼气容积/预计值均较治疗前改善（P〈0.05）;联合治疗组第1秒用力呼气容积、第1秒用力呼气容积/用力肺活量（FEV1/FVC）、第1秒用力呼气容积/预计值改善优于沙美特罗替卡松组、噻托溴铵组,差异有统计学意义（P〈0.05）。结论：沙美特罗替卡松粉吸入剂联合噻托溴铵粉吸入剂治疗慢性阻塞性肺疾病疗效肯定,优于单用一种药物治疗,值得临床进一步推广应用及探讨。     

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。     

噻托溴铵联合沙美特罗替卡松粉吸入剂吸入治疗中重度稳定期COPD的临床研究

目的探讨噻托溴铵联合沙美特罗替卡松粉吸人剂吸人治疗中重度稳定期慢性阻塞性肺疾病（COPD）的临床效果。方法回顾性分析57例中重度稳定期COPD患者的临床资料,将患者随机分为对照组（n=28,单用沙美特罗替卡松粉吸入剂治疗）和实验组（n=29,在对照组基础上加用噻托溴铵治疗）。治疗3个月后,比较两组的临床症状评分、肺功能指标的变化及不良反应发生率。结果治疗前,两组的临床症状评分、肺功能指标比较,差异无统计学意义（P〉0．05）;治疗3个月后,实验组的临床症状评分明显低于对照组,肺功能指标高于对照组,不良反应发生率显著低于对照组（P〈0．05）。结论中重度稳定期COPD应用噻托溴铵联合沙美特罗替卡松粉吸入剂吸入治疗可显著改善患者的临床症状和肺功能,不良反应少,值得临床推广。     

孟鲁司特钠联合沙美特罗氟替卡松治疗支气管哮喘患者的疗效观察

目的 研究孟鲁司特钠联合沙美特罗氟替卡松治疗支气管哮喘患者的效果。方法 采用前瞻性研究方法,选择2014年4月-2016年3月在四川省第四人民医院诊治的98例支气管哮喘患者作为研究对象,根据随机抽签原则把上述患者分为观察组与对照组各49例,对照组给予沙美特罗氟替卡松治疗,观察组给予孟鲁司特钠联合沙美特罗氟替卡松治疗,均治疗观察15d,比较两组临床疗效、肺功能及生活质量评分情况。结果 治疗后观察组总有效率为95.9%,明显高于对照组的81.6%,差异有统计学意义（P<0.05）。治疗后两组FEV1、FVC值和ACT评分都明显高于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）,且治疗后观察组以上指标明显高于对照组,组间比较差异有统计学意义（P<0.05）。治疗期间,两组不良反应率无统计学差异。结论 孟鲁司特钠联合沙美特罗氟替卡松治疗支气管哮喘患者能促进肺功能的改善,从而提高治疗疗效与生活质量。     

吸入沙美特罗/丙酸氟替卡松干粉治疗稳定期慢性阻塞性肺疾病疗效观察

目的观察吸入沙美特罗/丙酸氟替卡松干粉治疗稳定期慢性阻塞性肺疾病（COPD）的临床效果。方法 66例患者随机分为治疗组和对照组各33例。对照组给予口服一般平喘药,治疗组给予吸入沙美特罗/丙酸氟替卡松干粉治疗。观察2组肺功能和血气分析变化。结果 2组治疗后动脉血氧分压（PaO2）均升高,动脉血二氧化碳分压（PaCO2）均降低,第1秒用力呼气肺活量（FEV1）、FEV1占预计值百分比（FEV1%）及FEV1/用力呼气肺活量（FVC）均较治疗前升高,差异均有统计学意义（P〈0.05）。治疗组上述指标改善情况优于对照组,差异均有统计学意义（P〈0.05）。结论对COPD稳定期患者给予吸入沙美特罗/丙酸氟替卡松干粉剂治疗,可减轻COPD症状,改善肺功能,提高患者生命质量。     

Dose–response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate

AIMS: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). METHODS: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 microg day(-1), with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. RESULTS: Urine and serum cortisol were suppressed by 2000 microg FP and BDP vs placebo and by 1000 microg BDP vs placebo for urinary cortisol/creatinine (P < 0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 microg BDP vs 1000 microg FP (P < 0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol(-1) with BDP than FP at 1000 microg: n = 8/16 vs n = 2/16 (P < 0.05). CONCLUSIONS: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 microg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.     

Pharmacokinetics of epimeric budesonide and fluticasone propionate after repeat dose inhalation--intersubject variability in systemic absorption from the lung

AIMS: Pharmacokinetic variability is likely to be a significant factor contributing to the interindividual differences in dose requirements, anti-inflammatory response and side-effects with inhaled corticosteroids (ICS), but there is limited information about the disposition of ICS during regular dosing with a pressurized metered dose inhaler (pMDI). This study uses a mixed effects modelling approach to quantify and compare the interindividual variability in pharmacokinetics of epimeric budesonide (BUD) and fluticasone propionate (FP) after repeat-dose inhalation. METHODS: This pharmacokinetic substudy was part of a previously published open-label, randomised, placebo-controlled, 7-period crossover study to evaluate the short-term effects on plasma cortisol levels of inhaled BUD (400, 800, 1600 microg twice daily) and FP (375, 750, 1000 microg twice daily) via pMDI in a group of healthy male volunteers. On the fifth day of each high-dose treatment period (BUD 1600 microg twice daily and FP 1000 microg twice daily), venous blood samples were collected in nine subjects prior to the last dose and at 15 min, 30 min, 1, 2, 4, 6 and 8 h postdose for measurement of plasma drug concentrations to determine the pharmacokinetics of epimeric BUD and FP following inhalation. Non-compartmental analysis and a mixed effects model were used to characterize the disposition profiles. RESULTS: Both drugs had a rapid absorption half-life (BUD 10 min vs FP 11.3 min), but quite different elimination half-lives (BUD 2.4 h vs FP 7.8 h). Although there were intraindividual differences in the handling of the 22R-and 22S-epimers of BUD, there were no consistent pharmacokinetic differences between the two enantiomers in the group as a whole. Consistent with previous reports of FP's higher volume of distribution (V) and lower systemic bioavailability (F), the V/F ratio was lower for BUD than FP (498 l vs 8100 l). The parameter with the greatest interindividual variability for both BUD and FP was the rate of systemic absorption from the lung. CONCLUSIONS: This is the first report describing the pharmacokinetics of epimeric BUD and FP after repeat dose inhalation via pMDI. Three observations may be of clinical relevance: (1) there is considerable intersubject variability in the rate of absorption of both drugs from the lung; (2) in some individuals there was a long t(1/2),z for BUD, resulting in higher and more sustained plasma drug levels in the 4-12 h postdose period than would be predicted from single-dose pharmacokinetic data; and (3) there is evidence of diurnal variation in FP pharmacokinetics, with higher-than-expected plasma drug concentrations in the morning compared with the evening.     

沙美特罗替卡松粉吸入剂治疗慢性支气管炎的效果观察

目的评价沙美特罗替卡松粉吸入剂治疗慢性支气管炎的临床效果。方法选取2011年3月～2013年7月本院收治的慢性支气管炎患者97例,随机分为两组,其中观察组49例在吸氧、止咳平喘、保持呼吸道通畅、抗感染等常规治疗的基础上加用沙美特罗替卡松粉吸入剂,对照组48例仅采用慢性支气管炎常规治疗,2周后观察并比较两组患者的临床疗效和血气分析结果。结果观察组优32例（65．3％）,良15例（30．6％）,差2例（4．1％）,总优良数为47例（95．9％）;对照组优13例（27．1％）,良例27（56．3％）,差8例（16．7％）,总优良数为40例（83．3％）,观察组的临床疗效与对照组比较差异有统计学意义（P〈0．05）;观察组经过治疗PaCO2为（45．3±5．2）mmHg,PaO2为（88．1±7．5）mmHg,对照组PaCO2为（55．0±6．7）mmHg,PaO2为（71．9±6．8）mmHg,两组患者血气分析结果比较差异有统计学意义（P〈0．05）。结论沙美特罗替卡松粉吸人剂治疗慢性支气管炎的临床效果好,能有效提高患者的血氧饱和度,降低血中二氧化碳含量,值得临床推广。     

糠酸氟替卡松/维兰特罗复方剂治疗哮喘疗效与耐受性的Meta分析

目的 比较糠酸氟替卡松/维兰特罗复方剂（FF/VI）与吸入型糖皮质激素单药或联合长效β₂受体激动剂治疗哮喘患者的疗效与耐受性差异。方法 计算机检索CNKI、PubMed、Embase、Cochrane Library等数据库,纳入随机对照试验,采用Cochrane系统评价方法进行评价。结果 共纳入10个研究,共9 811例患者。在疗效上,FF/VI组与对照组相比,提高患者的1秒用力呼气量谷值[WMD=0.09,95% CI（0.05,0.13）,P=0.000]和哮喘控制测试评分[WMD=0.63,95% CI（0.24,1.03）,P=0.002]。在耐受性方面,FF/VI组与对照组相比不增加患者发生与治疗相关不良反应事件风险[RR=1.15,95% CI（0.98,1.36）,P=0.000]。结论 用FF/VI治疗哮喘在疗效方面具有优势,且具有良好的耐受性。其每日1次的用药频次可提高患者依从性,值得推荐使用。     

联合吸入治疗慢性阻塞性肺病稳定期患者的疗效观察

目的 观察联合吸入异丙托溴铵气雾剂和沙美特罗/替卡松粉吸入剂对慢性阻塞性肺病(COPD)稳定期患者的疗效.方法 采用随机、盲法、平行对照研究.将80例COPD患者随机分为观察组和对照组,疗程24周.观察组给予异丙托溴铵气雾剂和沙美特罗/替卡松粉吸入剂治疗,对照组给予异丙托溴铵气雾剂治疗.分别对两组患者治疗前后的临床症状...