Flumethasone targets the glucocorticoid receptor (GR). It is a highly selective and potent GR agonist. It effectively activates GR, leading to the inhibition of NF-κB and reduction of pro-inflammatory cytokines. It also acts as an agonist at mineralocorticoid receptors with EC50 values of 0.26 and 0.494 nM for GR and MR, respectively. The flumethasone/receptor complex binds to the nucleus and initiates genetic mechanisms.

The impact of one single therapeutic dose of flumethasone (0.5 mg/100 kg b.w.) on insulin sensitivity was studied in calves. Hyperinsulinemic, euglycemic clamp tests were performed before and after flumethasone treatment. At 24 h after treatment, insulin-dependent glucose utilization was reduced by 74% (P < 0.005). No significant changes occurred 72 h post-treatment.[1]

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In vitro, Flumethasone is a GR agonist with an EC50 of 0.26 nM for GR in CV-1 cells. It also has agonist activity at mineralocorticoid receptors with an EC50 of 0.494 nM. It inhibits NF-κB and reduces the production of pro-inflammatory cytokines. These in vitro studies confirm its mechanism as a glucocorticoid receptor agonist and its anti-inflammatory effects.

Cows were treated with 500 ml of 50% glucose solution. IV, and 40 mg of dexamethasone, IM (group 1), 40 mg of dexamethasone, IM (group 2), 5 mg of flumethasone (group 3), or 500 ml of 50% glucose solution, IV, and 5 mg of flumethasone (group 4). Treatment success was defined as recovery after a single treatment without relapse during the same lactation. Uterine disease (retained placenta or metritis), parity, and pretreatment plasma glucose, serum beta-hydroxybutyric acid, and urine acetoacetate concentrations were evaluated as possible confounding factors affecting recovery.[2]
In calves aged 3-3.5 months, a single intramuscular injection of flumethasone at 0.5 mg/100 kg body weight caused significant insulin resistance. At 24 h post-treatment, insulin-dependent glucose utilization (M) was reduced by 74% (P<0.005) compared to pre-treatment values, and the M/I index was reduced by 76% (P<0.005). Plasma glucose increased from 4.9±0.3 to 6.9±0.4 mmol/L (P<0.001), and plasma insulin increased from 3.5±0.3 to 20.0±7.1 μU/mL (P<0.005) at 24 h. At 72 h post-treatment, no significant changes in M, M/I index, glucose, or insulin were observed compared to baseline. [1]
In vivo, Flumethasone (0.5 mg/100 kg b.w.) reduces insulin-dependent glucose utilization in calves at 24 hours after treatment. It has anti-inflammatory, antipruritic, and vasoconstrictive properties. It is used topically for the treatment of various skin disorders. Its topical application minimizes systemic absorption and reduces the risk of systemic side effects. It is a well-established topical corticosteroid.

Non-cellular receptor binding assays for Flumethasone typically involve measuring its affinity for the glucocorticoid and mineralocorticoid receptors. These assays use purified receptor or cytosolic preparations and measure the displacement of a labeled ligand. Its binding affinity and potency as a GR agonist can be characterized. These experiments are essential for characterizing its receptor binding properties.

In vitro cell-based assays for Flumethasone are conducted using cells expressing the glucocorticoid receptor to assess its effects on gene expression and inflammation. Cells are treated with the compound, and the expression of glucocorticoid-responsive genes is measured by qPCR or reporter gene assays. Its effects on NF-κB activation and cytokine production can also be assessed. These experiments are crucial for confirming its mechanism of action.

Six male calves of Swedish Red and White breed, aged 3-3.5 months, were used. Flumethasone (0.5 mg per 100 kg body weight) was administered as a single intramuscular injection. Hyperinsulinemic euglycemic clamp tests were performed before treatment, at 24 h post-treatment, and at 72 h post-treatment. For the clamp test, a priming dose of insulin (3 mU/kg/min) was given during the first minute, then decreased every minute according to a predetermined schedule, and from the 10th minute insulin was infused at a constant rate of 1 mU/kg/min. Glucose infusion (100 mg/mL) started 5 minutes after insulin infusion. Blood samples were taken every 5 minutes for plasma glucose analysis, and the glucose infusion rate was adjusted to maintain plasma glucose at 4.5 mmol/L (the basal level for calves of this age). Plasma was collected every 30 minutes for insulin analysis. Total infusion time did not exceed 2 hours. The glucose infusion rate during the stable period (60-120 min) was used to calculate whole-body insulin-mediated glucose utilization (M) in μmol/kg/min. The M/I index was calculated as M divided by mean plasma insulin concentration during 60-120 min, multiplied by 100. [1]
In vivo animal studies for Flumethasone are typically conducted in animal models of skin inflammation to evaluate its topical efficacy. The compound is applied topically to the affected skin area, and its effects on inflammation, redness, and itching are assessed. Its systemic absorption and safety are also evaluated. These studies are essential for validating its in vivo efficacy as a topical corticosteroid.

Absorption, Distribution and Excretion
When applied topically, absorption, distribution, and excretion are minimal. Metabolism/Metabolites Primarily metabolized in the liver.

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Flumethasone has a molecular weight of 410.45 g/mol and a molecular formula of C22H28F2O5. It is a potent corticosteroid. It is applied topically, and its systemic absorption is minimal. Its pharmacokinetic properties are characterized by low systemic bioavailability. It is a prescription drug for the treatment of various skin disorders.

No adverse reactions were observed in calves following a single therapeutic dose of flumethasone (0.5 mg/100 kg b.w. intramuscular). [1]
Flumethasone has an established safety profile from its clinical use. It is generally well-tolerated when used topically. Common side effects include local skin reactions. Prolonged use may cause skin atrophy or other corticosteroid-related side effects. Comprehensive toxicological data are available from its clinical use. Flumethasone is an approved topical corticosteroid.

Zentralbl Veterinarmed A.1998 Sep;45(6-7):441-3;J Am Vet Med Assoc.1996 May 15;208(10):1702-4.

Flumethasone is a fluorinated corticosteroid belonging to the class of glucocorticoids, 11β-hydroxysteroids, 17α-hydroxysteroids, 21-hydroxysteroids, 20-oxosteroids, 3-oxo-Δ⁹Δ⁴-steroids, primary α-hydroxy ketones, and tertiary α-hydroxy ketones. It is an anti-inflammatory drug derived from the hydrogenation of pregnane. Flumethasone is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic, and vasoconstrictive effects. Because it is a salt compound, its anti-inflammatory effect is concentrated at the site of administration. This local application to the lesion site rapidly reduces inflammation, exudation, and itching. It is an anti-inflammatory glucocorticoid used in veterinary clinical practice. See also: Flumethasone pitavaate (its active ingredient)...see more...

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Drug Indications
For the treatment of contact dermatitis, atopic dermatitis, eczema, psoriasis, diaper rash, and other skin conditions. Mechanism of Action Flumethasone is a glucocorticoid receptor agonist. This complex binds to the cell nucleus, causing activation and inhibition of various genes. The anti-inflammatory effects of corticosteroids are thought to be related to lipocortin, a phospholipase A2 inhibitor that controls the biosynthesis of prostaglandins and leukotrienes by inhibiting arachidonic acid. Corticosteroids suppress the immune system by reducing lymphatic function, decreasing immunoglobulin and complement concentrations, inducing lymphopenia, and interfering with antigen-antibody binding. Flumethasone binds to plasma cortisol transporters, and its activity is enhanced when it is no longer bound to these transporters. Pharmacodynamics Flumethasone pitava is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic, and vasoconstrictive effects. As it is a private salt, its anti-inflammatory effect is concentrated at the site of application. This local action at the lesion site rapidly reduces inflammation, exudation, and itching.

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Glucocorticoids like flumethasone are widely used in the treatment of bovine ketosis. The glucose rise induced by glucocorticoids is likely a consequence of decreased glucose utilization due to decreased insulin sensitivity rather than increased gluconeogenesis. In ketosis, glucocorticoids reduce ketone body levels; the mechanism may involve reduced gluconeogenesis leading to increased mitochondrial Krebs cycle intermediates (e.g., oxalate, citrate), which increase cytosolic malonyl CoA, a suppressor of free fatty acid transport into mitochondria, thus reducing substrate availability for ketogenesis. [1]
Flumethasone (Flumetasone) is a moderately potent difluorinated corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. It is a highly selective and potent glucocorticoid receptor agonist that inhibits NF-κB and reduces pro-inflammatory cytokines. It is used topically for the treatment of skin disorders. Flumethasone is an approved drug.

C22H28F2O5

410.45

410.19

2135-17-3

16490

White to off-white solid powder

1.4±0.1 g/cm3

569.8±50.0 °C at 760 mmHg

237-240ºC

298.4±30.1 °C

0.0±3.6 mmHg at 25°C

1.579

1.61

3

7

2

29

839

9

C[C@@H]1C[C@H]2[C@@H]3C[C@@H](C4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)CO)O)C)O)F)C)F

WXURHACBFYSXBI-GQKYHHCASA-N

InChI=1S/C22H28F2O5/c1-11-6-13-14-8-16(23)15-7-12(26)4-5-19(15,2)21(14,24)17(27)9-20(13,3)22(11,29)18(28)10-25/h4-5,7,11,13-14,16-17,25,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1

(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 25.0 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: ≥ 2.5 mg/mL (6.09 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 25.0 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: ≥ 2.5 mg/mL (6.09 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 25.0 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.)