Comparison of Systemic Steroids

Drug Relative Equivalent Dose (mg) Relative Mineralo- corticoid Activity Duration (h) 

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The same qualitative results based on steric and electronic properties of the steroid ring system are found regardless of the structure of the peracid. Thus, although the generality of stereochemistry can be discussed with regard to all peracids, a quantitative comparison is valuable in some instances. 

C. Malcolmson, M. J. Lawrence, Comparison of the incorporation of model steroids into non-ionic micellar and microemulsion systems, J. Pharm. Pharmacol. 45 141 — 143 (1993). 

In the steroid field, a comparison of product ratios with those resulting from reductions with alkali metals reveals both similarities and differences, which led Dauben and co-workers [i] to postulate in 1956 that the observed stereochemical composition of products is a consequence of the interplay of two opposed factors. So successful was Dauben s treatment that it provided a virtually complete qualitative explanation of the relative proportions of axial and equatorial alcohols from reduction of each of the common steroid ketones. Dau-ben s approach developed from Barton s recognition in 1953 [46] that sterically unhindered ketones are reduced by complex hydrides as well as by metal/alcohol systems to give... 

Comparison of 17a-methyl-17)8-hydroxy-5a -androstano[3,2-r] pyrazole (D-l 1), 17a-methyl-17)8-hydroxyandrost-4-eno[3,2-c]pyrazole (A-157), and 17a-methyl-17/3-hydroxyandrost-4,6-dieno[3,2-c]pyrazole (A-168) showed that as the degree of unsaturation is increased there is a corresponding decrease in the anabolic and androgenic activities, with the last compound (A-168) having complete loss of these activities. It was suggested [124] that the anabolic and androgenic properties of this compound were lost due to the flattening imposed by the steroidal diene system. It was also found that introduction of an additional double bond between carbons 6 and 7 in 4-chlorotestosterone acetate (S-I48) results in the complete loss of activity (compare with S-146). 

The urinary excretion pattern of the 11-oxy-17-OS during the first few days bears more resemblance to that found in adults (Table 10), but again paper chromatography shows other compounds with similar polarity to be present (C6). The rate of excretion of a major unknown substance is given in Table 10, and it will be seen that the urinary content of this and of the known compounds rapidly decline over the first few days. The results shown were determined by scanning paper chromatograms stained with Zimmermann reagent. Identification of the named steroids was not complete and consisted of a comparison of 1 / values in various solvent systems before and after acetylation of the compounds. 

One impediment to straightforward comparison is the lack of solid-phase enthalpies of formation for most low molecular weight molecules. Examination of the few examples for which there are both solid- and liquid-phase values shows, however, that the liquid- and solid-phase enthalpies of reaction do not vary too much, at least within the uncertainties of the steroid combustion measurements. We are additionally hampered by not having available enthalpies of formation for those small molecules which most resemble the steroid substructure. The prototype small molecules required for the analysis are primarily those of substituted five- or six-membered carbocyclic rings. Although the functional groups on the available prototypes and the steroids are identical, stereochemical aspects (such as axial vs. equatorial substituent positions) and their consequent interactions are different due to the differences in conformational flexibility of the monocyclic and polycyclic systems. The prototype molecules and their liquid-phase enthalpies of formation are listed in Table 3. 

The most suitable method for the quantitative evaluation of the positive inotropic effect of a cardioactive steroid is at present the assessment of its influence on the isometric contraction curve, measiured in isolated papillary muscles. However, to obtain reliable data for the comparison of the inotropic potency of the various cardioactive steroids, it is important to perform the experiments under identical conditions [16]. Because of the variety of test conditions used, it is not easy or it is even impossible to compare the data reported in the literature [17,18]. A comprehensive survey of the structure-activity relationships found in guinea-pig left atria under identical conditions has recently been presented by R. Thomas and coworkers [19]. Therefore, this aspect will be mentioned here only with regard to the two basic risks for misinterpretation of pharmacological data from animal model systems. 

Brown PH, Matusiewicz SP, Shearing C, Tibi L, Greening AP, Crompton GK. Systemic effects of high dose inhaled steroids comparison of beclomethasone dipropionate and budesonide in healthy subjects. Thorax 1993 48 967-973. 

Fig. 8. Ultraviolet print of a narrow-strip paper chromatogram made for the preliminary evaluation of the steroid content of an extract of hog adrenal tissue. The top and bottom channels contained the six active adrenal steroids as comparison standards. The adrenal extract mixture was applied to the other channels in four concentrations as shown. The paper chromatogram was then developed in the toluene-propylene glycol system, for six hours at 26°C.

Returning to chloroform, the solvent which would best allow comparison of 22a with other systems, we discovered that the fluorescence spectrum of the receptor was affected by the presence of the glycosides. The changes were consistent with 1 1 complex formation, and could be analysed to give binding constants. As shown in Table 6, they confirmed the selectivity of 22a for /9-pyranosides, and clearly revealed its unusual potency. The new system binds 18 more strongly by two orders of magnitude than 16, the best of our steroid-based receptors. 

Wong and Hargreave (245) have written an excellent review about the bioequivalence of metered-dose inhaled medications. The article is written for comparisons of generic drugs with the original. It is, however, also relevant for comparison between different administration systems. The authors discuss the criteria for equivalence of medications in in vitro studies it should be close to 15% of the innovator. They also discuss the different main types of inhalation drugs (e.g., bronchodilators, steroids, and antiallergic aerosols). 

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