Fluticasone propionate

Fluticasone propionate is a high affinity, selective GR (glucocorticoid receptor) agonist which is derived from fluticasone used to treat asthma and allergic rhinitis.

Simultaneous analysis of glucocorticosteroid fluticasone propionate and its metabolite fluticasone propionate 17beta-carboxylic acid in human plasma by UPLC-MS/MS at sub pg/mL level.[Pubmed:27987390]

J Pharm Biomed Anal. 2017 Feb 20;135:1-7.

A highly sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of Fluticasone propionate (FP) and its major metabolite, Fluticasone propionate-17beta-carboxylic acid (FP 17beta-CA) in human plasma. The analytes and their deuterated internal standards, FP-d3 and FP 17beta-CA-d3 were extracted from 500muL plasma samples by solid phase extraction on Oasis MAX cartridges. The chromatographic analysis was performed on ACQUITY UPLC BEH C18 (50mmx2.1mm, 1.7mum) column using methanol-acetonitrile (50:50, v/v) and 2.0mM ammonium trifluroacetate (ATFA) (85:15, v/v) as the mobile phase. Following separation of the analytes, protonated precursor-->product ion transitions (FP: m/z 501.1-->293.2, FP17beta-CA: m/z 453.3-->293.2, FP-d3: m/z 504.2-->293.2, FP 17beta-CA-d3: m/z 456.3-->293.2) were monitored on FP 17beta-CA a triple quadrupole mass spectrometer, operating in multiple reaction monitoring (MRM) and positive ionization mode. The calibration curves were established in the range of 0.5-100pg/mL with a correlation coefficient (r(2))>/=0.9992 for both the analytes. The intra-batch and inter-batch accuracy and precision varied from 95.5-103.4% and 0.74-5.06% across quality controls for both the analytes. The mean assay recoveries for FP and FP 17beta-CA were 84.2% and 93.5% respectively. The validated method was successfully applied to support a bioequivalence study of 200mug FP, administered using nasal spray formulation in 18 healthy Indian subjects. Reproducibility of the method was assessed by reanalysis of 98 incurred study samples.

Olopatadine Hydrochloride and Fluticasone Propionate in Topical Treatment of Allergic Rhinitis: A Single Blind Randomised Study.[Pubmed:28208892]

J Clin Diagn Res. 2016 Dec;10(12):MC04-MC07.

INTRODUCTION: The use of corticosteroids or antihistaminics in treatment of allergic rhinitis is known and practiced since long. The efficacy of topical use of Fluticasone propionate and Olopatadine Hydrochloride (HCL) for symptomatic relief of allergic rhinitis has been studied either individually or with other drugs. But very few studies show comparison between these two drugs. AIM: To compare the efficacy of topical use of Fluticasone propionate and olopatadine hydrochloride for symptomatic relief of allergic rhinitis. DESIGN: In this single blind, randomized control study, the efficacy of topical use of olopatadine HCL was compared with Fluticasone propionate for relieving symptoms of allergic rhinitis. MATERIALS AND METHODS: The symptomatic cases were randomized in two groups for treatment using either olopatadine HCL or Fluticasone propionate respectively. In each group, the Total Symptom Scores (TSS) and individual symptom scores were recorded before and after treatment with the help of symptom evaluation scale. STATISTICAL ANALYSIS: Chi-square test, unpaired t-test, Mann Witney U-test, and Wilcoxon signed Rank test were used during analysis. The results of the comparison were noted and analysed. RESULTS: During four week study period both TSS and individual symptom score were reduced (p<0.05) in either groups. The TSS decreased by an average of 85.07% for those treated with olopatadine and by 95.55% for those treated with fluticasone. CONCLUSION: Overall Fluticasone propionate was superior to olopatadine in relieving symptoms of allergic rhinitis (p<0.005).

Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler versus a multi-dose inhaler in patients with chronic obstructive pulmonary disease.[Pubmed:28115223]

Pulm Pharmacol Ther. 2017 Apr;43:12-19.

BACKGROUND: This study tested the clinical non-inferiority of the Fluticasone propionate/salmeterol combination 50/250 mug (FSC) Rotacaps((R))/Rotahaler((R)) system, a single unit dose inhaler, with the multi-dose FSC Diskus((R)) inhaler in adults with chronic obstructive pulmonary disease (COPD). METHODS: This multi-centre, randomised, double-blind, double-dummy, two-way cross-over study compared 12 weeks' treatment of FSC administered twice daily using Rotacaps/Rotahaler or Diskus. The primary endpoint was change from baseline in trough morning forced expiratory volume in 1 s (FEV1) at Day 85, and the pre-defined non-inferiority criteria was: the lower limit of the confidence interval (CI) for the treatment difference (Rotacaps/Rotahaler-Diskus) in least squares (LS) mean change from baseline, being greater than -45 mL. Secondary endpoints included change in breathlessness (as measured by transition dyspnoea index (TDI)) and COPD-specific health status measures. RESULTS: The LS mean increase from baseline in trough FEV1 at Day 85 was 116 mL in the Rotacaps/Rotahaler group and 91 mL in the Diskus group (difference in model-adjusted LS mean change: 25 mL (95% CI 2 mL, 47 mL)), the lower limit of the CI for the treatment difference being greater than the protocol-defined criterion for non-inferiority i.e. -45 mL. Data for breathlessness, COPD-specific health status and safety parameters were similar following FSC treatment via either inhaler. CONCLUSIONS: This study demonstrated the clinical non-inferiority of FSC 50/250 mug when administered using Rotacaps/Rotahaler compared with Diskus in patients with COPD. The risk:benefit profile for the two inhalers was comparable.

Comparison of fluticasone propionate with budesonide administered via nebulizer: a randomized controlled trial in patients with severe persistent asthma.[Pubmed:28275486]

J Thorac Dis. 2017 Feb;9(2):372-385.

BACKGROUND: This study compared the efficacy and safety of Fluticasone propionate (FP) inhalation n solution with budesonide (BUD) suspension for inhalation administered via nebulizer, in Chinese adult patients with severe, persistent asthma. METHODS: This was a multicenter, randomized, active-controlled, single-blind, parallel-group study, conducted at 26 clinical sites in China. Participants were randomized 1:1 to FP nebules 1 mg twice daily or BUD 2 mg twice daily via nebulizer for 12 weeks. RESULTS: A total of 317 adult patients were randomized. The primary endpoint was mean change in morning peak expiratory flow (PEF) over weeks 1-12 from baseline, and analyzed in the ITT (n=315) and PP populations (n=283). Week 12 PEF increase from baseline was 26.7 L/min (14.1%) and 28.0 L/min (15.3%) in the ITT population, and 29.1 L/min (15.7%) and 30.1 L/min (16.2%) in the PP population, in the FP and BUD groups, respectively; all improvements were of clinical significance. Lower limits of the two-sided 95% CIs for the least squares (LS) mean treatment difference (FP minus BUD) were -12.19 L/min (ITT) and -12.95 L/min (PP), both above the pre-specified non-inferiority criteria -12.00 L/min and not clinically meaningful. There was no significant difference in the week 12 mean FEV1 increase between the FP and BUD groups (0.237 L/16.79% vs. 0.236 L/17.73%). Lower limits of the 95% CIs for LS mean treatment difference in morning PEF change from baseline over weeks 1-4 in a post hoc analysis were -10.41 and -11.96 L/min in the ITT and PP populations respectively; both above -12.00 L/min. A review of safety data indicated that rates of AEs, SAEs, and drug-related AEs were similar between two groups. CONCLUSIONS: The 12-week treatment of FP inhalation solution administered via nebulizer is safe and effectively for treating severe, persistent asthma in Chinese patients over 12 week.

Potentiation of the Kv1 family K(+) channel by cortisone analogues.[Pubmed:22803826]

ACS Chem Biol. 2012 Oct 19;7(10):1641-6.

The Kv1 family voltage-dependent K(+) channels are essential for termination of action potentials in neurons and myocytes. These channels form a stable complex with their beta subunits (Kvbeta), some of which inhibit channel activity. Cortisone potentiates Kv1 channel by binding to Kvbeta and promoting its dissociation from the channel, but its half-maximum effective concentration is approximately 46 muM. To identify corticosteroids that are more efficient than cortisone, we examined 25 cortisone analogues and found that Fluticasone propionate potentiates channel current with a half-maximum effective concentration (EC(50)) of 37 +/- 1.1 nM. Further studies showed that Fluticasone propionate potentiates channel current by inducing dissociation of Kvbeta, and docking of Fluticasone propionate into the cortisone binding site reveals potential interactions that enhance the EC(50) value. Thus, Fluticasone propionate provides a starting point for rational design of more efficient small-molecule compounds that increase Kv1 activity and affect the integrity of the Kv1-Kvbeta complex.

Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone.[Pubmed:11040338]

Eur J Pharmacol. 2000 Oct 20;406(3):325-32.

Beclomethasone, budesonide, dexamethasone, and Fluticasone propionate enhanced human eosinophil apoptosis in a concentration-dependent manner in vitro as assessed by flow cytometric analysis and morphological analysis. The order of potency was Fluticasone propionate (EC(50) 3.7+/-1.8 nM) approximately budesonide (EC(50) 5.0+/-1.7 nM)>beclomethasone (EC(50) 51+/-19 nM)>dexamethasone (EC(50) 303+/-40 nM). Hydrocortisone, prednisolone, and prednisone (up to 1 microM) did not induce any significant increase in eosinophil apoptosis. The apoptosis promoting effects of glucocorticoids on eosinophils were reversed by an antagonist of glucocorticoid receptor mifepristone. The survival-prolonging effect of tumor necrosis factor (TNF)-alpha was reversed by dexamethasone and fluticasone (1 microM). In contrast, fluticasone, and dexamethasone (1 microM) did not reverse the survival-prolonging effects of interleukins-3 and -5 or granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that fluticasone and budesonide induce eosinophil apoptosis at clinically achievable drug concentrations via an effect on glucocorticoid receptor.

The anti-inflammatory profile of fluticasone propionate.[Pubmed:7604948]

Allergy. 1995;50(23 Suppl):11-4.

Fluticasone propionate is a new corticosteroid based on the androstane nucleus. It is more lipophilic than beclomethasone dipropionate (BDP) and budesonide, and binds more avidly to human lung tissue. It has an absolute affinity (KD) of 0.5 nM for the glucocorticoid receptor and a relative receptor affinity 1.5- and 3.0-times greater than that of beclomethasone-17-monopropionate (17-BMP) and budesonide, respectively. The rate of association with the receptor is faster and the rate of dissociation slower than with standard corticosteroids. As a result, the half-life of the corticosteroid-receptor complex is > 10 h. Fluticasone propionate is also highly selective for the glucocorticoid receptor, with little or no activity at other steroid receptors. Pretreatment with Fluticasone propionate significantly inhibits the increase in mast cell numbers in the nasal mucosa of rats chronically exposed to toluene di-isocyanate (TDI), and suppresses TDI-induced mast cell degranulation. It is more potent in vitro than dexamethasone, BDP and budesonide in inhibiting anti-CD3-induced human T-lymphocyte proliferation, in attenuating tumour necrosis factor-alpha-induced endothelial cell adhesion molecule expression, and in increasing secretory leucocyte protease inhibitor levels in airway epithelial cells. It is also more potent and longer-acting than other corticosteroids in inhibiting oedema formation, interleukin-5 (IL-5)-induced blood eosinophilia, and IL-5- or platelet activating factor-stimulated eosinophil accumulation in the lung. Fluticasone propionate therefore has increased intrinsic glucocorticoid potency and high topical anti-inflammatory activity.

Fluticasone propionate is a high affinity, selective GR (glucocorticoid receptor) agonist which is derived from fluticasone used to treat asthma and allergic rhinitis.

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