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].

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].

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.

Absorption, Distribution and Excretion
The absorption and potency of any topical corticosteroid including betamethasone depends on the vehicle in which the steroid is delivered. For example, betamethasone dipropionate 0.05% ointment is classified as a highly potent topical steroid, while betamethasone dipropionate 0.05% cream or lotion is considered to be moderately potent. There are several structural modifications that can determine the potency of a topical corticosteroid. For example, corticosteroids containing a halogen at specific carbons, or that contain esters are more potent due to enhanced lipophilicity. As such, there is a marked difference between topical products containing betamethasone dipropionate vs. betamethasone valerate. Betamethasone dipropionate contains 2 esters which enhances its potency, while betamethasone valerate has only one ester and is less potent. It should be noted that the use of occlusive dressings with topical steroids significantly increases the absorption, increasing the risk for adverse effects.
Corticosteroids are eliminated predominantly in the urine.
In a study that included Indian women of reproductive age, the volume of distribution following a single intramuscular dose of betamethasone phosphate was 94,584±23,539 mL(s).
In a study that included Indian women of reproductive age, the CL/F following a single intramuscular dose of betamethasone phosphate was 6,466 ± 805 mL/hour.
Glucocorticoids ... absorbed systemically from sites of local administration, such as synovial spaces, the conjunctival sac, skin, and respiratory tract. When administration is prolonged, when the site of application is covered with an occlusive dressing, or when large areas of skin are involved, the absorption may be sufficient to cause systemic effects, including suppression of the HPA axis. /Adrenocorticalsteroids/
Following absorption, 90% or more of cortisol in plasma is reversibly bound to protein under normal circumstances. Only the fraction of corticosteroid that is unbound can enter cells to mediate corticosteroid effects. Two plasma proteins account for almost all of the steroid-binding capacity: corticosteroid-binding globulin (CBG; also called transcortin), and albumin. CBG is an alpha-globulin secreted by the liver that has high affinity for steroids but relatively low total binding capacity, whereas albumin, also produced by the liver, has low affinity but relatively large binding capacity. At normal or low concentrations of corticosteroids, most of the hormone is protein-bound. At higher steroid concentrations, the capacity of protein binding is exceeded, and a significantly greater fraction of the steroid exists in the free state. Corticosteroids compete with each other for binding sites on CBG. CBG has relatively high affinity for cortisol and most of its synthetic congeners and low affinity for aldosterone and glucuronide-conjugated steroid metabolites; thus, greater percentages of these latter steroids are found in the free form. /Adrenocortical Steroids/
The pharmacokinetics of betamethasone and its phosphate ester are described in 8 healthy adults after iv bolus injection of 10.6 mg betamethasone phosphate. Both cmpd were measured by high performance liquid chromatography with ultraviolet detection using sample handling methods which prevented hydrolysis of the ester in vitro. Betamethasone phosphate disappeared rapidly from plasma (mean half-life = 4.7 min) as betamethasone levels rose. Betamethasone plasma levels reached a peak 10-36 min after admin of the phosphate before declining in a biexponential manner. The terminal slow disposition phase had a mean half-life of 6.5 hr. Only about 5% of the dose was recovered from urine as betamethasone, indicating extensive extrarenal clearance of betamethasone. /Betamethason phosphate/

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Metabolism / Metabolites
The metabolism of betamethasone yields 6 metabolites. The metabolic processes include 6β hydroxylation, 11β-hydroxyl oxidation, and reduction of the C-20 carbonyl group followed by removal of the side chain.
All of the biologically active adrenocortical steroids and their synthetic congeners have a double bond in the 4,5 position and a ketone group at C 3. As a general rule, the metabolism of steroid hormones involves sequential additions of oxygen or hydrogen atoms, followed by conjugation to form water-soluble derivatives. Reduction of the 4,5 double bond occurs at both hepatic and extrahepatic sites, yielding inactive compounds. Subsequent reduction of the 3-ketone substituent to the 3-hydroxyl derivative, forming tetrahydrocortisol, occurs only in the liver. Most of these A ring-reduced steroids are conjugated through the 3-hydroxyl group with sulfate or glucuronide by enzymatic reactions that take place in the liver and, to a lesser extent, in the kidney. The resultant sulfate esters and glucuronides form water-soluble derivatives and are the predominant forms excreted in the urine. Neither biliary nor fecal excretion is of quantitative importance in human beings. /Adrenocortical Steroids/

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Biological Half-Life
In a study that included Indian women of reproductive age, the half-life following a single intramuscular dose of betamethasone phosphate was 10.2 ± 2.5 hours.
The pharmacokinetics of betamethasone and its phosphate ester are described in 8 healthy adults after i.v. bolus injection of 10.6 mg betamethasone phosphate. Both compounds were measured by high-performance liquid chromatography with ultraviolet detection using sample handling methods which prevented hydrolysis of the ester in vitro. Betamethasone phosphate disappeared rapidly from plasma (mean half-life = 4.7 min) as betamethasone levels rose. Betamethasone plasma levels reached a peak 10-36 min after administration of the phosphate before declining in a biexponential manner. The terminal slow disposition phase had a mean half-life of 6.5 hr.
Serum half-life of betamethasone is about 3 hr.

Interactions
Hyperglycemic action of cortisone /betamethasone/ may offset hypoglycemic effect of chlorpropamide...
Induction of hepatic enzymes by corticosteroids may increase the formation of a hepatotoxic acetaminophen metabolite, thereby increasing the risk of hepatotoxicity, when they are used concurrently with chronic or high-dose acetaminophen therapy. /Corticosteroid/
Risk of gastrointestinal ulceration or hemorrhage may be increased when these substances /alcohol or nonsteroidal anti-inflammatory drugs (NSAIDs)/ are used concurrently with glucocorticoids; however, concurrent use of NSAIDs in the treatment of arthritis may provide additive therapeutic benefit and permit glucocorticoids dosage reduction. /Corticosteroids/
Concurrent use /of carbonic anhydrase inhibitors/ with corticosteroids may result in severe hypokalemia and should be undertaken with caution; serum potassium concentrations and cardiac function should be monitored during concurrent use. /Corticosteroids/
For more Interactions (Complete) data for BETAMETHASONE (25 total), please visit the HSDB record page.

[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 Agents; Anti-Inflammatory Agents, Steroidal; Glucocorticoids, Synthetic; Glucocorticoids, Topical
/Indicated for the treament of/ allergic disorders: drug induced allergic reactions; angioedema; acute noninfectious laryngeal edema; allergic, perennial or seasonal, severe rhinitis; serum sickness; urticarial transfusions reactions.
/Indicated for the treament of/ collagen disorders: acute, rheumatic or nonrheumatic carditis; systemic lupus erythematosus; mixed connective tissue disease; polyarteritis nodosa; relapsing polychondritis.
/Indicated for the treatment of/ dermatologic disorders: alopecia areata; atopic dermatitis; contact dermatitis; exfoliative dermatitis; herpetiformis, bullous dermatitis; severe, seborrheic dermatitis; severe inflammatory dermatoses; severe multiforme erythema; granuloma annulare; keloids; lichen planus; lichen simplex chronicus; discoid lupus erythematosus; mycosis fungoides; necrobiosis lipoidica diabeticorum; pemphigus; severe psoriasis; psoriatic plaques; severa eczema; pemphigoid; localized cutaneous sarcoid.
For more Therapeutic Uses (Complete) data for BETAMETHASONE (16 total), please visit the HSDB record page.

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Drug Warnings
... The most striking effects of corticosteroids on the cardiovascular system result from mineralocorticoid-induced changes in renal Na + excretion as is evident in primary aldosteronism. The resultant hypertension can lead to a diverse group of adverse effects on the cardiovascular system, including increased atherosclerosis, cerebral hemorrhage, stroke, and hypertensive cardiomyopathy. The mechanism underlying the hypertension remains incompletely understood, but restriction of dietary Na + can lower the blood pressure considerably. /Adrenocorticosteroids/
Two effects of corticosteroids on lipid metabolism are firmly established. The first is the dramatic redistribution of body fat that occurs in settings of hypercorticism such as Cushing's syndrome. The other is the permissive facilitation of the effect of other agents, such as growth hormone and beta-adrenergic receptor agonists, in inducing lipolysis in adipocytes, with a resultant increase in free fatty acids following glucocorticoid administration. /Adrenocorticosteroids/
...Caution should be exercised if fluorinated preparations are used on face or other cosmetically important areas, since paradoxical eruptions may occur with long-term use.
Although injection may be given intra-articularly, it must be remembered that repeated intra-articular glucocorticoids sometimes effect painless destruction of joint.
For more Drug Warnings (Complete) data for BETAMETHASONE (34 total), please visit the HSDB record page.

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Pharmacodynamics
Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

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.)