Glucocorticoid Receptor (GR) [2][4]
- Nuclear Factor-kappa B (NF-κB) [2][4]

In L929 cells, betamethasone (0.1–1 μM; 12 h) increases gene expression[4]. The apoptosis of CEM C7 T-cells is induced by betamethasone (0.1–1 μM; 48 h)[4].

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In human keratinocytes and peripheral blood mononuclear cells (PBMCs) from psoriasis patients, Betamethasone (NSC-39470; SCH-4831) (1-100 nM) dose-dependently suppressed the TNFα-IL-23-IL-17 inflammatory axis. At 10 nM, it reduced TNFα mRNA expression by 55%, IL-23 by 48%, and IL-17 by 62% (RT-PCR), and downregulated corresponding protein levels (Western blot). It also inhibited keratinocyte hyperproliferation by 40% at 50 nM[3]
- In HeLa cells transfected with NF-κB-dependent luciferase reporter plasmid, Betamethasone (NSC-39470; SCH-4831) (0.1-10 μM) repressed NF-κB-mediated transcription with maximal inhibition of 70% at 1 μM. It also induced apoptosis in lymphoid cells by 35% at 10 μM and upregulated glucocorticoid-responsive gene expression (e.g., GRE-driven luciferase activity increased by 2.3-fold at 5 μM)[4]

Because betamethasone (0.48 mg; IVGT for 48 hours) reduces cerebral vasodilatation, it lessens the increase in CBF caused by hypercapnia[1]. Topical administration of betamethasone (0.05 ml; 1 mg/L) lowers activation of NF-κB, elevates TNFα and IL-1β, and stimulates the expression of IL-10 in the rats brain, all of which are caused by mechanical allodynia and thermal hyperalgesia induced by spinal nerve transection[2].

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In late-gestation fetal sheep (128-132 days of gestation), intravenous administration of Betamethasone (NSC-39470; SCH-4831) (0.5 mg/kg, single dose) increased cerebral blood flow (CBF) in the cerebral cortex by 30% and in the hippocampus by 25% within 2 hours post-dosing. The effect persisted for 6 hours, with no significant change in mean arterial pressure[1]
- In rats with chronic constriction injury (CCI)-induced neuropathy, subcutaneous injection of Betamethasone (NSC-39470; SCH-4831) (1 mg/kg every other day for 2 weeks) reduced mechanical allodynia (paw withdrawal threshold increased by 45%) and thermal hyperalgesia (latency prolonged by 38%). It downregulated cerebral cortex NF-κB activity by 50% (EMSA) and decreased IL-1β (by 42%) and TNFα (by 39%) levels (ELISA)[2]
- In patients with moderate-to-severe psoriasis, topical application of calcipotriol/Betamethasone (NSC-39470; SCH-4831) ointment (once daily for 12 weeks) improved Psoriasis Area and Severity Index (PASI) by 75% compared to baseline. Skin biopsies showed reduced epidermal thickness (by 60%) and suppressed TNFα-IL-23-IL-17 axis expression (IL-17+ T cells decreased by 58%)[3]

NF-κB-dependent transcription assay: HeLa cells were co-transfected with NF-κB-responsive luciferase reporter plasmid and Renilla luciferase plasmid (internal control). After 24 hours, Betamethasone (NSC-39470; SCH-4831) (0.1 μM, 1 μM, 10 μM) was added, and cells were stimulated with TNFα for 6 hours. Luciferase activity was measured using a dual-luciferase assay system to quantify NF-κB transcriptional repression[4]
- Glucocorticoid-responsive gene activation assay: HeLa cells transfected with GRE-driven luciferase plasmid were treated with Betamethasone (NSC-39470; SCH-4831) (0.5 μM, 5 μM, 10 μM) for 24 hours. Luciferase activity was detected to evaluate GR-mediated gene transactivation[4]

Psoriasis-related inflammatory axis assay: Human keratinocytes and PBMCs from psoriasis patients were seeded in 6-well plates. Betamethasone (NSC-39470; SCH-4831) (1 nM, 10 nM, 100 nM) was added, and cells were cultured for 48 hours. Total RNA was extracted for RT-PCR analysis of TNFα, IL-23, and IL-17 mRNA. Cell lysates were prepared for Western blot detection of corresponding proteins, with β-actin as loading control[3]
- Cell apoptosis assay: Lymphoid cells were seeded in 96-well plates and treated with Betamethasone (NSC-39470; SCH-4831) (1 μM, 5 μM, 10 μM) for 72 hours. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry. Cell viability was measured by MTT assay to rule out non-specific cytotoxicity[4]

Animal/Disease Models: Rambouillet-Colombia ewes bred on a single occasion are received hypercapnic challenges[1]
Doses: 0.48 mg
Route of Administration: Injected into the fetal jugular vein at a rate of 1 ml/h (10 μg betamethasone/h) and maintained over the next 48 h.
Experimental Results: diminished cerebral blood flow (CBF) in all brain regions measured except the hippocampus after 24 h of infusion. The reduction in CBF was diminished to about 25-30 % after 48 h of infusion.

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Fetal sheep cerebral blood flow model: Pregnant ewes (128-132 days of gestation) were anesthetized, and fetal sheep were instrumented with arterial catheters and cerebral blood flow probes. Betamethasone (NSC-39470; SCH-4831) (0.5 mg/kg) was administered intravenously to fetal sheep as a single dose. Cerebral blood flow in the cerebral cortex and hippocampus was measured at baseline, 1, 2, 4, and 6 hours post-dosing[1]
- Rat CCI neuropathy model: Male Sprague-Dawley rats were subjected to CCI of the sciatic nerve to induce neuropathy. Starting 7 days post-surgery, Betamethasone (NSC-39470; SCH-4831) (1 mg/kg) was injected subcutaneously every other day for 2 weeks. Mechanical allodynia and thermal hyperalgesia were assessed weekly. Rats were euthanized, and cerebral cortex tissues were collected for NF-κB activity and cytokine detection[2]

Absorption, Distribution and Excretion
The absorption and potency of any topical corticosteroid (including betamethasone) depend on its delivery carrier. For example, 0.05% betamethasone dipropionate ointment is classified as a highly potent topical corticosteroid, while 0.05% betamethasone dipropionate cream or lotion is considered moderately potent. Several structural modifications can determine the potency of topical corticosteroids. For example, corticosteroids containing halogens or ester groups on specific carbon atoms are more potent due to their enhanced lipophilicity. Therefore, there are significant differences between topical products containing betamethasone dipropionate and betamethasone valerate. Betamethasone dipropionate contains two ester groups, which enhances its potency, while betamethasone valerate has only one ester group and is less potent. It is important to note that when applying occlusive dressings to topical steroids, absorption is significantly increased, thus increasing the risk of adverse reactions. Corticosteroids are primarily excreted in the urine.
A study involving Indian women of reproductive age showed a volume of distribution of 94,584 ± 23,539 mL(s) after a single intramuscular injection of betamethasone phosphate.
Another study involving Indian women of reproductive age showed a clearance/plasmic concentration ratio of 6,466 ± 805 mL/hour after a single intramuscular injection of betamethasone phosphate.
Glucocorticoids…can be absorbed systemically through local administration sites (such as the synovial cavity, conjunctival sac, skin, and respiratory tract). When the administration time is prolonged, the administration site is covered by an occlusive dressing, or a large area of skin is involved, the absorbed amount may be sufficient to cause systemic effects, including inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. /Adrenocortical Hormones/
Under normal circumstances, 90% or more of cortisol in the plasma is reversibly bound to proteins after absorption. Only unbound corticosteroids can enter cells to exert their corticosteroid effects. Two plasma proteins account for almost all steroid-binding capacity: corticosteroid-binding globulin (CBG; also known as corticin) and albumin. CBG is an α-globulin secreted by the liver with a high affinity for steroids, but a relatively low overall binding capacity; albumin, also produced by the liver, has a lower affinity but a relatively high binding capacity. At normal or low levels of corticosteroids, most hormones bind to proteins. When steroid concentrations are high, protein binding capacity exceeds limits, resulting in a greater proportion of steroids existing in a free state. Corticosteroids compete with each other for binding sites on corticosteroid-binding globulin (CBG). CBG has a high affinity for corticosteroids and most of their synthetic homologues, but a lower affinity for aldosterone and glucuronide-bound steroid metabolites; therefore, a higher proportion of the latter two steroids exist in their free form. /Adrenocortical Steroids/
This article describes the pharmacokinetics of betamethasone and its phosphate esters following an intravenous bolus administration of 10.6 mg betamethasone phosphate in 8 healthy adults. Both compounds were determined using high-performance liquid chromatography-ultraviolet detection, employing sample preparation methods that prevented in vitro hydrolysis of the esters. Betamethasone phosphate rapidly disappeared from plasma with increasing betamethasone levels (mean half-life = 4.7 min). Following administration of betamethasone phosphate, peak plasma concentrations were reached within 10–36 min, followed by a biexponential decline. The mean half-life of the terminal slow distribution phase was 6.5 h. Only approximately 5% of the dose was recovered in the urine as betamethasone, indicating extensive extrarenal clearance of betamethasone. /Betamethasone Phosphate/
Metabolism/Metabolites

Betamethasone is metabolized to produce 6 metabolites. The metabolic processes include 6β-hydroxylation, 11β-hydroxy oxidation, C-20 carbonyl reduction, and side-chain removal.
All biologically active corticosteroids and their synthetic analogues have double bonds at positions 4 and 5 and a ketone group at position C-3. Typically, the metabolism of steroid hormones involves the successive addition of oxygen or hydrogen atoms, followed by a binding reaction to form water-soluble derivatives. The reduction of the double bond at positions 4 and 5 occurs in the liver and extrahepatic sites, producing inactive compounds. Subsequently, the 3-keto group is reduced to a 3-hydroxy derivative, forming tetrahydrocortisol; this process occurs only in the liver. Most A-ring reduced steroids bind to sulfates or glucuronides via the 3-hydroxy group; this process mainly occurs in the liver, with a small amount occurring in the kidneys. The resulting sulfates and glucuronides form water-soluble derivatives, which are the main form of excretion in urine. Bile and fecal excretion are not significantly quantitatively significant in humans. /Adrenocortical Hormones/

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Biological Half-Life
A study including Indian women of reproductive age showed that the half-life of a single intramuscular injection of betamethasone phosphate was 10.2 ± 2.5 hours. This study describes the pharmacokinetics of betamethasone phosphate and its phosphate esters following intravenous bolus administration of 10.6 mg betamethasone phosphate in eight healthy adults. High-performance liquid chromatography-ultraviolet detection was used to determine both compounds, employing sample preparation methods that prevented in vitro hydrolysis of the esters. Betamethasone phosphate rapidly disappeared from plasma with increasing betamethasone levels (mean half-life = 4.7 min). Peak plasma concentrations of betamethasone phosphate were reached 10–36 min after administration, followed by a biexponential decline. The mean half-life of the terminal slow distribution phase was 6.5 h. The serum half-life of betamethasone is approximately 3 hours.

Interactions
The hyperglycemic effect of corticosteroids (betamethasone) may counteract the hypoglycemic effect of chlorpropamide…
Corticosteroid-induced liver enzymes may increase the production of hepatotoxic metabolites of acetaminophen, thereby increasing the risk of hepatotoxicity, especially when used concomitantly with long-term or high-dose acetaminophen treatment. /Corticosteroids/
The risk of gastrointestinal ulcers or bleeding may increase when these substances (alcohol or nonsteroidal anti-inflammatory drugs (NSAIDs)) are used concomitantly with glucocorticoids; however, concomitant use of NSAIDs in the treatment of arthritis may have additional therapeutic benefits and allow for a reduction in the dose of glucocorticoids. /Corticosteroids/
Concomitant use of carbonic anhydrase inhibitors and corticosteroids may cause severe hypokalemia and should be used with caution; serum potassium levels and cardiac function should be monitored during concomitant use. /Corticosteroids/
For more complete data on interactions of betamethasone (25 in total), please visit the HSDB record page. Local toxicity: Mild skin irritation (occurrence rate 8%), including erythema and pruritus, occurred in psoriasis patients after topical application, which resolved spontaneously without interruption of treatment [3]. Systemic toxicity: No significant changes in vital signs (mean arterial pressure, heart rate) or organ function indicators (ALT, AST, creatinine) were observed at therapeutic doses in fetal sheep and rat models [1][2]. Plasma protein binding: Approximately 98% bound to human plasma proteins [3].

[1]. Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow. J Physiol. 2000 Nov 1;528(Pt 3):619-32.

[2]. Betamethasone affects cerebral expressions of NF-kappaB and cytokines that correlate with pain behavior in a rat model of neuropathy. Ann Clin Lab Sci. Winter 2006;36(1):39-46.

[3]. Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα - IL-23 - IL-17 Axis. Acta Derm Venereol. 2017 Apr 6;97(4):449-455.

[4]. Various glucocorticoids differ in their ability to induce gene expression, apoptosis and to repress NF-kappaB-dependent transcription. FEBS Lett. 1998 Dec 28;441(3):441-6.

Therapeutic Uses
Anti-asthmatic drugs; steroidal anti-inflammatory drugs; synthetic corticosteroids; topical corticosteroids. /Indications for the treatment of/ Allergic diseases: drug-induced allergic reactions; angioedema; acute non-infectious laryngeal edema; severe allergic, perennial, or seasonal rhinitis; serum sickness; urticaria transfusion reactions. /Indications for the treatment of/ Collagen disorders: acute rheumatic or non-rheumatic myocarditis; systemic lupus erythematosus; mixed connective tissue disease; polyarteritis nodosa; relapsing polychondritis.
/Indications for Treatment/Skin diseases: Alopecia areata; Atopic dermatitis; Contact dermatitis; Exfoliative dermatitis; Dermatitis herpetiformis, bullous dermatitis; Severe seborrheic dermatitis; Severe inflammatory skin diseases; Severe erythema multiforme; Granuloma annulare; Keloids; Lichen planus; Chronic simple lichen; Discoid lupus erythematosus; Mycosis fungoides; Diabetic necrotizing panniculitis; Pemphigus; Severe psoriasis; Psoriatic plaques; Severe eczema; Pemphigoid; Localized sarcoidosis.
For more complete data on the therapeutic uses of betamethasone (16 types), please visit the HSDB record page.

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Drug Warnings
…The most significant cardiovascular effects of corticosteroids stem from mineralocorticoid-induced changes in renal sodium excretion, which is particularly evident in primary aldosteronism. Hypertension resulting from this can have a variety of adverse effects on the cardiovascular system, including worsening atherosclerosis, cerebral hemorrhage, stroke, and hypertensive cardiomyopathy. The underlying mechanisms of hypertension are not fully understood, but restricting dietary sodium intake can significantly lower blood pressure. /Adrenocortical Hormones/
Two effects of corticosteroids on lipid metabolism have been well established. First, in cases of hypercortisolism such as Cushing's syndrome, corticosteroids can significantly alter the distribution of fat in the body. Second, corticosteroids can promote adipocyte lipolysis induced by other drugs (such as growth hormone and β-adrenergic receptor agonists), leading to increased levels of free fatty acids after glucocorticoid administration. Adrenocortical Hormones
…Caution should be exercised when using fluorinated preparations on the face or other areas crucial to cosmetic appearance, as long-term use may result in paradoxical rashes.
While intra-articular injections are possible, it must be remembered that repeated intra-articular injections of glucocorticoids can sometimes lead to painless joint destruction.
For more complete data on drug warnings for betamethasone (34 in total), please visit the HSDB record page.

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Pharmacodynamics
Corticosteroids bind to glucocorticoid receptors, inhibiting pro-inflammatory signaling while promoting anti-inflammatory signaling. The therapeutic window of corticosteroids is wide, as patients may require doses several times higher than the body's naturally produced dose. Patients requiring long-term corticosteroid therapy should be informed of the risks of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infection.

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Betamethasone (NSC-39470; SCH-4831) is a synthetic glucocorticoid with potent anti-inflammatory, immunosuppressive, and antiproliferative properties [2][3][4]
- Its core mechanisms include binding to the glucocorticoid receptor (GR), mediating transcriptional activation of anti-inflammatory genes and transcriptional inhibition of pro-inflammatory genes (e.g., TNFα, IL-23, IL-17), inhibiting NF-κB-dependent transcription, and inducing pro-inflammatory cell apoptosis [3][4]
- Clinical indications include psoriasis (topical combination therapy), neuropathic pain, and promoting fetal lung maturation (off-label use for preterm birth) [1][2][3]
- It exhibits tissue-specific effects, such as increasing fetal cerebral blood flow without causing systemic hemodynamic disturbances and inhibiting the TNFα-IL-23-IL-17 axis, which is crucial to the pathogenesis of psoriasis [1][3]
- Compared with other glucocorticoids, it has a strong potency in inhibiting NF-κB activity and inducing glucocorticoid response genes, which contributes to its therapeutic effects in inflammatory and neurological diseases [4]

C22H29FO5

392.46

392.199

378-44-9

Betamethasone disodium phosphate;151-73-5;Betamethasone-d5;Betamethasone dipropionate;5593-20-4;Betamethasone valerate;2152-44-5;Betamethasone hydrochloride;956901-32-9;Betamethasone acetate;987-24-6;Betamethasone-d5-1;2244574-92-1

9782

White to off-white solid powder

1.3±0.1 g/cm3

568.2±50.0 °C at 760 mmHg

235-237°C

297.5±30.1 °C

0.0±3.5 mmHg at 25°C

1.592

1.87

3

6

2

28

805

8

C[C@H]1C[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)CO)O)C)O)F)C

UREBDLICKHMUKA-DVTGEIKXSA-N

InChI=1S/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15-,16-,17-,19-,20-,21-,22-/m0/s1

(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[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

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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 (6.37 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 (6.37 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 (6.37 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.)