Efficacy and safety of mometasone furoate nasal spray in nasal polyposis

BACKGROUND: Studies have suggested that topical corticosteroids are effective in the treatment of nasal polyps; however, this has yet to be confirmed in a large, robust clinical trial. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) for nasal polyposis. METHODS: A total of 354 subjects with bilateral nasal polyps and clinically significant congestion/obstruction participated in this multinational, randomized, double-blind, placebo-controlled study. Subjects received MFNS 200 microg once or twice daily or placebo for 4 months. Coprimary endpoints were (1) change from baseline to last assessment in physician-evaluated bilateral polyp grade score and (2) change from baseline averaged over month 1 in subject-assessed nasal congestion/obstruction. ANOVA was used for all efficacy endpoints, except for change in bilateral polyp grade score, for which baseline polyp grade was added as a covariate. RESULTS: Compared with placebo, MFNS 200 microg administered once or twice daily produced significantly greater reductions in bilateral polyp grade score (P < .001, P = .010, respectively) and congestion/obstruction (P = .001, P < .001), as well as improvement in loss of smell (P < .001, P = .036), anterior rhinorrhea (P < .001 for both), and postnasal drip (P < .001, P = .001) over month 1. MFNS 200 microg twice daily was superior to MFNS 200 microg once daily in reducing congestion/obstruction (P = .039), and there were more improvers in the MFNS 200 microg twice daily group (P = .035). MFNS was well tolerated in both groups. CONCLUSION: MFNS 200 mug, once or twice daily, was safe and significantly superior to placebo in reducing polyp grade (size and extent) and improving congestion/obstruction and return of sense of smell. MFNS is an effective medical treatment for nasal polyposis and may reduce or delay the need for surgery.     

Mometasone furoate monohydrate nasal spray for the treatment of nasal congestion in allergic rhinitis

Allergic rhinitis (AR) affects an estimated 20–40 million Americans annually. It is a multifaceted condition comprising a range of symptoms, including nasal congestion, arguably the most bothersome symptom. Of the various types of medications available for the treatment of AR, intranasal corticosteroids are considered the most effective. Mometasone furoate nasal spray is an intranasal corticosteroid with anti-inflammatory properties. It is indicated for the treatment of the nasal symptoms of seasonal AR and perennial AR in adults and children, for the prophylaxis of nasal symptoms of seasonal AR and for the treatment of nasal polyps. Numerous clinical trials have demonstrated that mometasone furoate nasal spray effectively relieves nasal congestion in adults and children with AR, while providing excellent safety and tolerability.     

Mometasone furoate inhibits growth of acute leukemia cells in childhood by regulating PI3K signaling pathway

Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer before the age of 15 years, seriously endangering the health of children. The main treatment for Childhood ALL was pharmacotherapy. But these drugs have many side effects and some of them could develop drug resistance quickly. Mometasone furoate (MF) is an efficient glucocorticoid for topical treatment of inflammation on the skin, lung and nose.

Methods: In this study, we investigated whether the MF had effects on ALL cells proliferation and migration.

Results: The CCK-8 proliferation test showed that the cell viability was the lowest at 25?nM MF treatment and the increased OD value was time-dependent. In transwell assay, the number of CCRF-CEM cells was reduced in MF treated group. We found the expression of anti-apoptotic protein bcl-2 decreased the expression of pro-apoptotic protein caspase3 and bax increased in CCRF-CEM cell line treated with MF. The expression of p-AKT, p-mTOR, p70S6?K, vascular endothelial growth factor and CyclinD1 were decreased in MF treated group.

Conclusion: This study reveals that MF can inhibit proliferation and invasion/migration and induce apoptosis in Childhood ALL cells, which may be regulated by Phosphatidylinositol 3-kinase signaling pathway. These results suggest MF may be a potential new drug target for clinical ALL treatment.     

Formulation of a novel fixed dose combination of salmeterol xinafoate and mometasone furoate for inhaled drug delivery

Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6 months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC_0–24h) of two APIs were higher for the BMP combination group exhibiting a significantly higher lung concentration of drugs than for the crystalline physical blend. While high system drug levels are generally undesirable in lung targeted therapies, high blood levels in this rodent study could be indicative of increased pulmonary tissue exposure using BMP formulations.     

鼻用糠酸莫米松治疗儿童 OSAHS的临床疗效观察

目的 探讨鼻用糠酸莫米松治疗儿童阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)的疗效。方法 选取我院扁桃体轻中度肥大的儿童OSAHS患者50例,给予糠酸莫米松鼻内局部应用1个月。治疗前后均进行睡眠呼吸紊乱儿童的家长问卷(obstructive sleep apnea-18,osa-18)调查和纤维鼻咽喉镜检查。结果 治疗前后osa-18问卷得分和腺样体的大小差异均有统计学意义(P=0.001)。结论 对于病程较短的扁桃体轻中度肥大的OSAHS患儿,给予糠酸莫米松鼻内应用,可有效减少腺样体体积缓解临床症状,在儿童OSAHS治疗中起着重要作用。     

卡泊三醇搽剂联合糠酸莫米松乳膏序惯疗法治疗头皮银屑病临床疗效观察

目的观察卡泊三醇搽剂联合糠酸莫米松乳膏序惯疗法治疗头皮银屑病的疗效及安全性。方法 62例头皮银屑病患者,采用随机对照的方法分为治疗组和对照组,每组31例。治疗组采用卡泊三醇搽剂联合糠酸莫米松乳膏序贯疗法治疗,对照组采用卡泊三醇搽剂治疗。比较两组患者临床疗效、皮损面积评分,并分析其不良反应发生情况。结果治疗2周后,治疗组有效率为45.16%,对照组有效率为32.26%,两组比较差异无统计学意义(χ2=1.09, P>0.05)。治疗4周后,治疗组有效率为67.74%,高于对照组的41.94%,差异有统计学意义(χ2=4.17, P<0.05)。治疗6周后,治疗组有效率87.10%显著高于对照组的64.52%,差异有统计学意义(χ2=4.31, P<0.05)。两组患者治疗前及治疗2周后皮损面积评分比较差异无统计学意义(P>0.05);治疗4、6周后,治疗组患者的皮损面积评分均低于对照组,差异具有统计学意义(P<0.05)。两组患者在治疗过程中均未见严重不良反应,治疗组中2例(6.45%)患者出现局部皮肤轻微烧灼感和疼痛,对照组中2例患者(6.45%)自觉局部轻微灼热不适和疼痛,均未影响治疗,未予处理。结论卡泊三醇搽剂联合糠酸莫米松乳膏序惯疗法治疗头皮银屑病疗效好,安全性高。     

鼻渊通窍颗粒联合糠酸莫米松鼻喷雾剂治疗儿童过敏性鼻炎的临床研究

目的探讨鼻渊通窍颗粒联合糠酸莫米松鼻喷雾剂治疗儿童过敏性鼻炎的临床疗效。方法选取2017年8月—2018年10月在广东省妇幼保健院就诊的110例过敏性鼻炎患儿作为研究对象,按照随机数字表法将全部患者分为对照组和治疗组,每组各55例。对照组睡前鼻吸入糠酸莫米松鼻喷雾剂,2揿/鼻孔,1次/d。治疗组在对照组治疗的基础上温水口服鼻渊通窍颗粒,15 g/次,3次/d。两组患者均连续治疗8周。观察两组的临床疗效,比较两组的临床症状体征、血清因子指标。结果治疗后,对照组和治疗组的总有效率分别为78.18%、92.73%,两组比较差异具有统计学意义(P0.05)。治疗后,两组的喷嚏、鼻塞、流涕、鼻痒、体征评分均明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后,治疗组的喷嚏、鼻塞、流涕、鼻痒、体征评分均低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组的嗜酸粒细胞阳离子蛋白(ECP)、免疫球蛋白E(IgE)、血清细胞间黏附分子-1(ICAM-1)水平均显著降低,同组治疗前后差异具有统计学意义(P0.05);且治疗后,治疗组的ECP、IgE、ICAM-1水平均低于对照组,两组比较差异具有统计学意义(P0.05)。结论鼻渊通窍颗粒联合糠酸莫米松鼻喷雾剂治疗儿童过敏性鼻炎具有较好的临床疗效,可改善临床症状体征,降低ECP、IgE、ICAM-1水平,具有一定的临床推广应用价值。     

A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects

AIMS

This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate(FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.

METHODS

This was a randomized, placebo-and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 μg) or placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF(4000 μg), oral moxifloxacin (400 mg) or placebo.

RESULTS

There was a lack of effect of FF/VI (200/25 μg) on QTcF (Fridericia''s correction); all time-matched mean differences from baseline relative to placebo (0–24 h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100 μg, FF/VI had no significant clinicaleffect on QTcF except at 30 min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0–24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative toplacebo of >10 ms (1–8 h postdose).

CONCLUSIONS

Repeat once-daily dosing of FF/VI (200/25 μg), which is the highest therapeutic strength used in phase III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100 μg) demonstrated a small transient effect on QTcF but not on QTci.     

变异性鼻炎应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗的效果观察

目的探究变异性鼻炎应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗的效果。方法本次研究资料选取时间段为2019年8月至2020年8月,患者为我院诊治的96例变异性鼻炎患者。经随机数字表法予以分组,其中参照组(48例)行糠酸莫米松鼻喷雾剂治疗,观察组(48例)行通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗。比较两组临床疗效及症状、体征情况与不良反应发生情况等。结果相较参照组,观察组治疗总有效率更高,不良反应发生率更低(P<0.05)。两组治疗后临床症状、体征评分均比治疗前低,且观察组比参照组低(P<0.05)。结论变异性鼻炎患者应用通窍鼻炎片联合糠酸莫米松鼻喷雾剂治疗效果确切,利于患者疗效提高、症状改善及不良反应发生率降低,可行推广。