Prednisolone 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. 

Suspension. If the drug is not sufficiently soluble, it can be formulated as a suspension. A suspension may also be desired to improve stability, bioavailability, or efficacy. The major topical ophthalmic suspensions are the steroid anti-inflammatory agents prednisolone acetate, dexamethasone, fluorometholone, and rimex-olone. Water-soluble salts of prednisolone phosphate and dexamethasone phosphate are available however, they have a lower steroid potency and are poorly absorbed. 

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. 

Metabolites (Activity) beclomethasone 17-mono-propionate (active), free beclome-thasone (very weak anti-inflammatory effects) 16 -hydroxy-prednisolone and 6 -hydroxy-budesonide (< 1 % of parent) 67-OH (low corticosteroid potency) ... 

The inclusion of an a-methyl group in position 6 of prednisolone will yield 6-a-methylprednisolone, a compound with slightly greater glucocorticoid potency. This small structural modification greatly diminishes the binding of methylprednisolone to transcortin. 

Additional double bonds. A -componnds (where A indicates the position of a double bond) were introduced, like prednisone (3.7), a A -ll-ketone, and prednisolone, its 11-hydroxy analogne. Changing the geometry of the A ring increased the potency without augmenting mineralocorticoid activity. 

The increase in potency observed in the progestin series by incorporation of additional unsamration in the A ring (see delmadinone, (5-4) obtains in the corticoid series as well the majority of commercial steroid anti-inflamatories in fact include this feamre. The double bond at the 1 position may be formed by fermentation with an organism such as Corynebacterium simplex [11] or by reaction with selenium dioxide. Hydrocortisone acetate (13-4) yields the widely used corticoid prednisolone acetate (14-1) in the same vein, cortisone acetate (13-5) goes to prednisone acetate (14-2). Mild saponification of either of these products yields the free alcohols prednisolone and prednisone, respectively. 

The fluorinated glucocorticoids are said to have relatively more catabolic activity than others and might have a greater effect on the skeleton but such impressions may merely reflect the general potency of some newer glucocorticoids and a tendency to use them in inappropriate doses. A relatively new glucocorticoid, deflazacort, has been proposed to have less effect on bone metabolism, but a double-blind study has failed to show an advantage compared with prednisolone (SEDA-21, 417 194). 

Introduction of the 16a-hydroxyl group into 9-fluoro-hydrocortisone and 9-fluoro-prednisolone has been shown by Bernstein et al. [16] to result in complete suppression of the salt-retaining properties of these steroids, without appreciably impairing their glucocorticoid activity. Moreover, studies in man have demonstrated the anti-arthritic activity of 9-fluoro-16a-hydroxy-prednisolone and have confirmed its lack of salt-retaining activity. Subsequently, Lederle reported that the anti-inflammatory potency was lowered, but salt retention was eliminated. 

Inhaled corticosteroids are minimally absorbed and have a local effect. However, depending on the dose and potency of the inhaled corticosteroid, inhaled forms can produce systemic side-effects. Oral prednisolone is rapidly absorbed and is metabolised by the liver. Some corticosteroids may be administered intravenously. 

The mere introduction of a double bond transforms hydrocortisone to prednisolone, a big biological change see Table 34.1 for relative potencies 1.0 1.0 to 4 0.8. 

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... 

Depending on the location of ocular inflammation, a specific corticosteroid in a specific dosage form may be chosen. For instance, a corticosteroid of high potency, such as prednisolone acetate, fiuorometholone, or dexamethasone, may be chosen for deep-seated inflammation of the uveal tract. Further treatment of such inflammation may take the form of subtenon injections or oral (systemic) administration of selected corticosteroids, depending on the indication and the dosage forms available. For inflammation of a more superficial nature, the lower strengths of prednisolone acetate or the lower-potency corticosterioids, such as hydrocortisone or medrysone, will usually be chosen. 

Further optimization at Merck [77] improved the potency similar to that of prednisolone (Figure 9.13). The depicted benzothiophene derivative shows dissociation in vitro and in vivo. Inversion of the hydroxyl methyl bridge stereochemistry... 

On a weight-for-weight basis, the antirheumatic potency of triamcinolone is greater than that of prednisolone (-20%) and approximately the same as that of methylprednisolone. Initial improvement following administration of triamcinolone is similar to that noted with other compounds. Reports in the literature, however, indicate that the percentage of patients maintained satisfactorily for long periods has been distinctly smaller than that with prednisolone. 

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