Corticosteroid activity

The basic concept behind studies such as this is that esterification may modify corticosteroid activity by (1) increasing lipid solubility of the drug and thereby... 

Figure 2 Design and metabolism of soft corticosteroids (1) based on the inactive metabolite approach. The acid metabolites (2, 3) are inactive, but suitable substitution at the 17a-hydroxy and 17(5-carboxy functions (R h R2) can restore corticosteroid activity and also allow facile one-step deactivation. Loteprednol etabonate (4), a soft steroid, is an active anti-inflammatory compound that lacks the IOP-elevating side effect of the other steroids used ophthalmically.

Sangalang, G.B. and J.F. Uthe. Corticosteroid activity, in vitro, in interrenal tissue of Atlantic salmon (Salmo salar) parr. 1. Synthetic profiles. Gen. Comp. Endocrinol. 95 273-285, 1994. 

The ICSs beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide that are currently available for use are compared and listed in Table 26-12. The ICSs have pharmacokinetic differences that result in different topical/ systemic activity. Most evidence is consistent with log-linear dose-response curves for both indirect and direct responses. The log-linear nature of the dose-response curve for corticosteroid activity raises the issue of how much of a difference in dose (or lung delivery) or potency is detectable. The dose-response curves for the ICSs are relatively flat primarily because all the measures used to assess efficacy (lung function, BHR, symptoms, and as-needed short-acting inhaled /32-agonist use) are downstream events from the anti-inflammatory activity. In general, it takes a fourfold difference in potency or dose to detect clinically significant differences. The table of comparative doses (see Table 26-12) is based on extensive comparative clinical trials. Clinical comparative doses take into consideration potency differences as well as lung delivery differences from the various devices. 

Hydrocortisone (24) (Ri, R, R Xj, X, = H, no A Fig. 15.10) undergoes a variety of oxidative and reductive metabolic conversions (115). Oxidation of its dihydroxyacetone side-chain leads to formation of cortienic acid (25) through a 21-aldehyde (21-dehydrocortisol) and a 21 -acid (cortisolicacid). Cortienic acid is an ideal lead for the inactive metabolite approach because it lacks corticosteroid activity and is a major metabolite excreted in human urine. To obtain active compounds,the important pharmacophores found in the 17a and 17P side-chains had to be restored. Suitable isosteric/isoelectronic substitution of the a-hydroxy and /3-carboxy substituents with esters or other types of functions should restore the original corticosteroid activity and also incorporate hydrolytic features to help avoid accumulation of toxic levels. More than 120 of such soft steroids (24) that resulted from modifications of the 17/3-carboxyl function and the 17o -hydroxy function together with other... 

The sulfacetamide sodium and prednisolone acetate ophthalmic ointment USP is a sterile topical ophthalmic ointment combining an antibacterial and a corticosteroid. Active ingredients are sulfacetamide sodium 10% and... 

Bethamethason cream in this case however there is firstly the choice between valerate and dipropionate, each of which represents a different corticosteroid activity class. Then in both cases the desired concentration in relation to the amount of free betamethasone has to be calculated. The strength of the authorised products is specified respectively as valerate or dipropionate. 

Kidney JC, Cockcroft DW, Hargreave FE, Boulet LP, Jennings B. Evaluation of inhaled corticosteroid activity using single doses and allergen challenge model. J Allergy Chn Immunol 1997 100 65-70. 

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