Betamethasone potency

The natural compounds cortisol [50-23-7], cortisone [53-06-5], and corticosterone [50-22-6] vary only slightly in stmctures and pharmacologic properties (see Steroids). The synthetic analogues inmore modem practice, prednisolone [52438-85-4], dexamethasone [50-02-2], triamcinolone [124-94-7], and betamethasone have greater antiinflammatory potency, and their effects on sodium retention tend to be less severe. 

Betamethasone is a fluorinated steroid. Fluorination is substitution with an electron-attracting group and increases potency. 

Two further communications [31,32] reported that prednisolone stearoylglycollate, in substantial doses, was the least potent anti-inflammatory steroid (among the representative series studied) with respect to pituitary-adrenal inhibition. The order of increasing suppressive potency in this test was prednisolone stearoylglycollate, prednisolone, triamcinolone, dexamethasone, betamethasone. Techniques used in the comparative evaluations included the metyrapone test and gas-liquid chromatography. 

Hydroxylation or methylation at the 16 position of a-fluoroprednisolone to give triamcinolone, dexam-ethasone, or betamethasone increases antiinflammatory potency and drastically diminishes sodium-retaining... 

Research teams at Glaxo then undertook the synthesis of derivatives of betamethasone that might afford superior local anti-inflammatory and anti-allergic effectiveness. Using McKenzie and Stoughton s [21] new human-based pharmacologic test that could identify with ease the relative topical potency of steroid inflammatory compounds, a series of 17-esters of betamethasone prepared by Elks [22] was evaluated. This resulted in compounds with new standards of topical potency such as triamcinolone acetonide and fluocinolone acetonide. It was then discovered, that potency peaked with betamethasone-17-valerate and betamethasone-17,21-dipropionate, which were between four- and ten-fold more potent than the standard. 

Anti-inflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical anti-inflammatory compounds were 17a-heterocyclic esters in the 16a-methyl series where the 21-substit-uent was either chloro or fluoro. Thus, [21-chloro-17-(2 -furoate)] was eight-fold more potent than betamethasone valerate, while [21-fluoro-17-(2 -furoate)], [21-chloro-17-(2 -thenoate)] and 6a-fluoro-21-chloro-17-(2 -furoate)] were three-fold as potent as betamethasone valerate. 

The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic-pituitary-adrenal axis suppression, leading to clinically significant adrenal insufficiency or Cushing s syndrome, is infrequent. Two patients developed adrenal suppression after the unregulated use of betamethasone dipropionate 0.05% ointment (about 80 g/week) or clobetasol 0.05% ointment (up to 100 g/week), obtained without prescription to treat psoriasis (362). 

The anti-inflammatory potencies of betamethasone and dexamethasone exceed that of prednisolone. However, because of the facility with which prednisolone acetate crosses the cornea, a 1% solution is generally regarded as the drug of choice for the topical treatment of anterior uveitis in the horse, although comparable clinical results can be achieved using 0.1% dexamethasone in alcohol preparations. The frequency of application of topical glucocorticoids is largely determined by the severity and the nature of the clinical problem... 

Topical corticosteroids are the most widely used agents in the treatment of psoriasis in the United States. They are often used to decrease erythema, scaling, and pruritus. Topical vasoconstricting potencies of corticosteroids are ranked by the Stoughton-Cornell classification in seven classes (Table 96-4). Class I steroids are very high-potency products such as clobetasolpropionate 0.05%, halobetasolpropionate, and betamethasone dipropionate. ... 

Therapeutic index the ratio of the relative potency for the ED50 to the relative potency for the TED50 betamethasone 17a-valerate has been arbitrarily assigned a value of 1. 

In the case of ester derivatives the degree of esterification (i.e., mono or diesters) and the size of the esterifying acid helps to determine the extent of lipophilicity of the product. Thus betamethasone 17-valerate (Table 14-1) would be expected to be more soluble in CHC13 (1 2) than the 21 -acetate (1 16), which in turn is more lipid soluble than the alcohol (1 325). Topical antiinflammatory potency parallels such values. 

The treatment of ocular inflammations due to allergy, following eye surgery or other causes, also respond well to topical (ocular) therapy, thereby avoiding much of the systemic toxicity. It is interesting that the lower-potency hydrocortisone (acetate) suspension is less likely to precipitate glaucoma symptoms than the more potent dexa- and betamethasone, which tend to raise intraocular pressure. 

Hydrocortisone has relatively low potency. In contrast, betamethasone has very high potency. Prednisone is intermediate. 

Newer synthetic glucocorticoids have incorporated chlorine atoms onto the steroid molecule as fluorine substitutes. Beclomethasone, a 9a-chloro analogue of betamethasone, is a potent glucocorticoid with approximately half the potency of its fluoro analogue. It is used topically as its dipropionate derivative in inhalation aerosol therapy for asthma and rhinitis (see Inhaled and Intranasal Glucocorticoids) but not for treatment of steroid-responsive dermatoses (77). The topical anti-inflammatory potency for beclomethasone... 

All absorbable corticoids possess the ability to produce adrenal suppression [11, 76]. The degree of suppression is related to potency. Comparative quantitative studies employ the Food and Drug Association s (FDA) diseased-skin protocol. As little as 14 g per week of clobetasol has induced suppression. Optimized betamethasone diproprionate is somewhat less suppressive, requiring over 49 g per week to significantly reduce plasma cortisol. Incomplete data with difluorosone suggests that it may be less suppressive. Fortunately, plasma cortisol usually returns to normal within 3 days when the superpotents are discontinued, at least in short-time application studies. 

The con aratlve topical anti-inflammatory potency of 31 to betamethasone 17-valerate was directly related to the formulation used. ... 

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