Lung fibroblasts that have been isolated from the lung are prevented from activating by flunisolide (0.1–10 μM, 1 hour) [1]. Flunisolide (10 μM, 24 hours) causes sputum eosinophils to undergo apoptosis and decreases the release of MMP-9, TIMP-1, TGF-β, and fibronectin from sputum cells isolated from individuals with mild to moderate asthma [2]. In BEAS-2B cells, flunisolide (0.1–10 µM µM, 24 hours) efficiently suppresses TNF-α-induced ICAM-1 expression as well as GM-CSF and IL-5 production [3]. It has been demonstrated that flunisolide (115 µM, 0–3 hours) is ATP-dependent and can move polarizedly in Calu-3 cells from the apical (ap) to the basolateral (bl) direction [4].

In silicosis mice, flunisolide (intranasal treatment, 0.3–10 µg/mouse, daily, commencing on days 21–27) enhances the rate of silicon particle clearance in the lungs while simultaneously inhibiting lung inflammation, fibrosis, and airway hyperresponsiveness [1]. The intranasal administration of flunisolide (0.3–10 µg/mouse, daily, days 21–27) prevents the formation of macrophages and myofibroblasts in lung tissue caused by silica [1].

Apoptosis analysis [2]
Cell Types: eosinophils
Tested Concentrations: 10 μM
Incubation Duration: 24 h
Experimental Results: Induced apoptosis of sputum eosinophils.

Animal/Disease Models: Male Swiss-Wechsler mouse (intranasal instillation, crystalline silica, 10 mg/50 µL, particle size 0.5-10 µm) [1]
Doses: 0.3-10 µg/mouse daily, day 21 -27-day intranasal administration
Experimental Results: diminished granulomatous reactions, collagen deposition associated with granuloma formation induced by silica particles. Reduce the number of F4/80 and α-SMA positive cells.

Absorption, Distribution and Excretion
Absorbed rapidly

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Metabolism / Metabolites
Primarily hepatic, converted to the S beta-OH metabolite.

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Biological Half-Life
1.8 hours

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although not measured, the amounts of inhaled corticosteroids absorbed into the maternal bloodstream and excreted into breastmilk are probably too small to affect a breastfed infant. Expert opinion considers inhaled, nasal and oral corticosteroids acceptable to use during breastfeeding.
◉ Effects in Breastfed Infants
None reported with any corticosteroid.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Approximately 40% after oral inhalation

[1]. Intranasal Flunisolide Suppresses Pathological Alterations Caused by Silica Particles in the Lungs of Mice. Front Endocrinol (Lausanne). 2020 Jun 17;11:388.

[2]. In vitro effects of flunisolide on MMP-9, TIMP-1, fibronectin, TGF-beta1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics. Allergy. 2004 Sep;59(9):927-32.

[3]. Modulation by flunisolide of tumor necrosis factor-alpha-induced stimulation of airway epithelial cell activities related to eosinophil inflammation. J Asthma. 2010 May;47(4):381-7.

[4]. Evidence of P-glycoprotein mediated apical to basolateral transport of flunisolide in human broncho-tracheal epithelial cells (Calu-3). Br J Pharmacol. 2001 Dec;134(7):1555-63.

Flunisolide can cause developmental toxicity and female reproductive toxicity according to state or federal government labeling requirements.
Flunisolide is a fluorinated steroid, a cyclic ketal, a 20-oxo steroid, a 21-hydroxy steroid, an 11beta-hydroxy steroid, a 3-oxo-Delta(1),Delta(4)-steroid and a primary alpha-hydroxy ketone. It has a role as an immunosuppressive agent, an anti-inflammatory drug and an anti-asthmatic drug.
Flunisolide (marketed as AeroBid, Nasalide, Nasarel) is a corticosteroid with anti-inflammatory actions. It is often prescribed as treatment for allergic rhinitis and its principle mechanism of action involves activation of glucocorticoid receptors.
Flunisolide anhydrous is a Corticosteroid. The mechanism of action of flunisolide anhydrous is as a Corticosteroid Hormone Receptor Agonist.
Flunisolide is a synthetic corticosteroid with antiinflammatory and antiallergic properties. Flunisolide is a glucocorticoid receptor agonist that binds to cytoplasmic glucocorticoid receptors and subsequently translocates to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both are potent mediators of inflammation.

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Drug Indication
For the maintenance treatment of asthma as a prophylactic therapy.
FDA Label

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Mechanism of Action
Flunisolide is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flunisolide binds to plasma transcortin, and it becomes active when it is not bound to transcortin.

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Pharmacodynamics
Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms.

C24H31FO6

434.4977

434.21

3385-03-3

Flunisolide hemihydrate;77326-96-6;Flunisolide-d6

82153

White to off-white solid powder

1.33g/cm3

581.8ºC at 760mmHg

237-240°C (dec.)

305.7ºC

2.274

2

7

2

31

910

9

C[C@]12C[C@@H]([C@H]3[C@H]([C@@H]1C[C@@H]4[C@]2(OC(O4)(C)C)C(=O)CO)C[C@@H](C5=CC(=O)C=C[C@]35C)F)O

XSFJVAJPIHIPKU-XWCQMRHXSA-N

InChI=1S/C24H31FO6/c1-21(2)30-19-9-14-13-8-16(25)15-7-12(27)5-6-22(15,3)20(13)17(28)10-23(14,4)24(19,31-21)18(29)11-26/h5-7,13-14,16-17,19-20,26,28H,8-11H2,1-4H3/t13-,14-,16-,17-,19+,20+,22-,23-,24+/m0/s1

(1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

NasarelFlunisolideBronalideLunisAeroBidNasalideSynaclyn

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~287.69 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)