403 ForbiddenThey are designed for health professionals to use. You may prednisolone equivalent doses the Oral Steroids article more useful, or one of our other health articles. Hydrocortisone cortisol is secreted by the adrenal cortex and has both glucocorticoid and mineralocorticoid effects. The term 'glucocorticoid' prednisolone equivalent doses from the early discovery ai during steroid cycle these hormones were important in glucose metabolism. Since the s synthetic glucocorticoids have been developed for their anti-inflammatory and immunomodulatory effects. Attempts have been made to increase the beneficial effects and reduce the adverse effects by modifying the equivlent nucleus and side groups. A brief outline of complex steroid biosynthesis and prednisolone equivalent doses is helpful when considering the therapeutic benefits and adverse effects of the glucocorticoids.
Corticosteroid Dose Equivalents: Corticosteroid Dose Equivalents
Deflazacort is a synthetic corticosteroid characterized by a favourable pharmacokinetic profile, peculiar pharmacodynamic properties and a good safety profile.
However, to the best of our knowledge, no dose-conversion table based on direct comparison of relative potencies between deflazacort and other main corticosteroids is currently available in scientific literature. This paper, while reporting a brief review of deflazacort pharmacological properties, its efficacy and tolerability in different clinical areas, has been designed with the specific aim of providing a new dose-conversion table of corticosteroids, including for the first time also deflazacort.
We suggest that this new conversion table could be a useful tool for physicians who need to select the appropriate dose of deflazacort in their clinical practice. Corticosteroids are hormones with 21 carbon atoms; they are secreted by the adrenal cortex and are traditionally divided into two main groups: This distinction is based on their preferential biological activity, i. The main glucocorticoid produced by the adrenal cortex is cortisol also known as hydrocortisone ; the main mineralocorticoid hormone is aldosterone.
The potency of corticosteroids on carbohydrate metabolism is closely related to their anti-inflammatory potency, as the activation of the same glucocorticoid receptor is responsible for both metabolic and anti-inflammatory effects. Relative potencies of main corticosteroids modified from [ 1 ]. However, classification of corticosteroids into glucocorticoids and mineralocorticoids should not be seen as a strict rule; for example, it has been shown that corticosteroids classified in one group can also perform, in addition to their specific biological activities, certain activities that are typical of the other group, although to a lesser extent.
Accordingly, some steroids predominantly classified as glucocorticoids, such as cortisol and prednisone a synthetic corticosteroid , also have a moderate, but significant, mineralocorticoid activity; similarly, fludrocortisone, a synthetic corticosteroid with a high mineralocorticoid potency, also exhibits a moderate glucocorticoid activity [ 1 ]. Furthermore, activation of glucocorticoid receptor or mineralocorticoid receptor in the human body does not rely only on the structure of the drugs, but also on additional factors, including drug metabolism by beta-hydroxydehydrogenase enzyme, which then can affect drug concentration both in the bloodstream and target tissues.
The anti-inflammatory action of corticosteroids is the main reason for their use as therapeutic agents. In its early stages, the scientific research on corticosteroids was oriented towards the synthesis of novel compounds characterized by a higher anti-inflammatory potency than cortisone, with a lower incidence of side effects. This initially led to the development of synthetic glucocorticoids, such as prednisolone and prednisone, characterized by a higher anti-inflammatory potency than natural steroids, with a mineralocorticoid activity reduced approximately by a half.
Subsequently, other corticosteroids were synthetized, including fluorinated glucocorticoids such as dexamethasone. Even though these drugs are devoid of mineralocorticoid activity, some typical adverse events associated with their prolonged use have been reported. For example, safety issues are relevant in children and adolescents, where steroid therapy may result in behavioral disturbances and growth retardation due to a not yet fully understood mechanism, which probably involves abnormalities in GH release , and in elderly patients, where the risk of steroid side effects may be enhanced by the frequent presence of comorbidities requiring pharmacological polytherapy.
More recently, other corticosteroids, including deflazacort, have been synthetized with the main aim of making available new agents that are better tolerated in each age group. Deflazacort is a heterocyclic corticosteroid, oxazoline-derivative of prednisolone [ 2 ], characterized by high efficacy and good tolerability, as demonstrated by the results of several clinical studies that have evaluated its therapeutic activity and safety in conditions where corticosteroid treatment is indicated.
Presently, extensive clinical experience has been gained on the efficacy of deflazacort in rheumatic diseases in adults and children, as well as in respiratory, renal, and hematologic diseases. However, to the best of our knowledge, no complete dose-conversion table, based on direct comparisons of the relative potencies of deflazacort and other commonly used corticosteroids, is currently available in scientific literature.
In this paper, we briefly review some of the most relevant clinical trials on deflazacort, showing its efficacy and tolerability; furthermore, we propose a new table for the conversion of corticosteroid doses, elaborated from available literature data, including both deflazacort and other common steroids used in clinical practice.
Deflazacort is a synthetic corticosteroid, characterized by the insertion of a methyl-oxazoline ring in the chemical structure of prednisolone acetate [ 3 ] Fig. Chemical structures of prednisolone and deflazacort [ 3 ]. After oral administration, deflazacort is rapidly and completely absorbed in the intestinal tract peak plasma concentration is reached within 1—2 hours.
Subsequently, deflazacort is deacetylated at position 21 to form the main active metabolite, i. Glucocorticoids have immunosuppressive and anti-inflammatory properties, both primarily related to the antagonism of specific leukocyte functions and to the inhibition of the synthesis of pro-inflammatory cytokines.
In vitro, deflazacort significantly inhibits both the proliferation of mononuclear cells derived from human peripheral blood, and the release of inflammatory cytokines by these cells. Deflazacort is also able to inhibit chemotaxis, superoxide anion generation and chemiluminescence of human polymorphonuclear leukocytes in vitro [ 3 ].
Studies carried out using different experimental models indicate that deflazacort is an effective inhibitor of the early exudative phase of inflammation, as well as of the development of chronic granulomatous inflammation. Furthermore, deflazacort has been shown to inhibit experimentally-induced chronic inflammatory articular disease i. Studies carried out to evaluate glucocorticoids ability to induce glycogen deposition in the liver of surrenectomized rats have shown that deflazacort is able to increase gluconeogenesis and hepatic glycogen synthesis, with a potency of action about 10 times higher than prednisolone administered at equivalent doses.
The anti-inflammatory potency of deflazacort is about 10—20 times higher than prednisolone and 40 times higher than cortisol hydrocortisone. Furthermore, the duration of action of deflazacort anti-inflammatory effects is longer than other glucocorticoids administered at equivalent doses [ 6 ].
Deflazacort has proven to be effective in the treatment of various rheumatological disorders including: A clinical study, which evaluated deflazacort ability to exert a protective effect on bone erosion and joint damage, typical of RA, has shown that deflazacort is able to inhibit, in a dose-dependent manner, the invasiveness and the proliferation of synoviocytes collected both from patients with RA and healthy volunteers through differential modulation of single components of the fibrinolytic system [ 10 ].
Deflazacort is indicated in steroid treatment of bronchial asthma and in the exacerbations of Chronic Obstructive Pulmonary Disease COPD , to control inflammation and increased bronchial reactivity, which are the basis of bronchospasm. Patients were evaluated at the start of treatment visit 1 , on day 2 visit 2 and on day 7 visit 3.
Two children out of the 54 enrolled were hospitalized on visit 2 one from each group. Further improvement was observed on visit 3, i.
Reproduced with permission from [ 11 ]. Peak Expiratory Flow Rate. In summary, deflazacort and prednisolone demonstrated similar efficacy in improving pulmonary function and clinical symptoms in the treatment of children with moderate exacerbations of asthma [ 11 ]. Some clinical trials, conducted both in adult and pediatric populations, have evaluated the use of deflazacort in patients undergoing renal transplantation and in patients with nephrotic syndrome.
Lean body mass decreased by approximately 2. The study concluded that, in kidney-transplanted patients, the use of deflazacort is associated with lesser loss of lumbar spine BMD and whole body BMD compared to prednisone; deflazacort also helps to prevent fat accumulation and lipid profile worsening [ 12 ]. Another randomized, double-blind study compared the effects of treatment with deflazacort 0.
The results of this study showed that the maintenance therapy with deflazacort, in comparison with methylprednisone maintenance therapy, is associated with an improved linear growth and also prevents excessive bone loss and fat accumulation in the population of pre-puberal patients [ 13 ].
Nephrotic syndrome, characterized by hypoproteinaemic edema in association with extensive proteinuria, may occur as a result of several underlying kidney diseases, the most common of which are minimal lesion glomerulonephritis and membranous glomerulonephritis.
It is known that corticosteroid therapy increases the rate of spontaneous remission in patients with minimal lesion nephrotic syndrome, and has beneficial effects also in focal and segmental glomerulosclerosis. Clinical trials have demonstrated the efficacy of deflazacort treatment in both adult and pediatric patients with nephrotic syndrome.
Two clinical trials found that deflazacort was at least as effective as prednisone in adult patients with idiopathic nephrotic syndrome during a 3-month crossover study as well as in patients with minimal change, membranoproliferative, focal segmental or membranous glomerulonephritis during a month double-blind parallel study [ 3 ]. A clinical complication of nephrotic syndrome is hypogammaglobulinemia due to increased catabolism and urinary loss of immunoglobulin which is associated with a higher risk of infections, mainly caused by encapsulated bacteria.
In this respect, some evidence indicate that IgG2-subclass antibodies are protective against this type of microorganisms, so that their loss in nephrotic syndrome is a risk factor for infection. In both treatment groups, a similar return to normal levels of total IgG and IgG1 was observed, but only those patients treated with deflazacort showed a significant improvement in the IgG2 and IgG3 subclasses values [ 14 ].
Another distinctive feature of deflazacort is its smaller influence on carbohydrate metabolism than other glucocorticoids, as demonstrated in both studies conducted on animal models [ 4 ] and in clinical trials [ 17 , 18 ].
Furthermore, the risk of sodium retention and hypokalemia, related to the mineralocorticoid activity of the drug, is greatly reduced with deflazacort in comparison with older synthetic steroids [ 3 ].
Because of its low liposolubility, only a small part of desacetyl-deflazacort, biologically active metabolite of deflazacort , crosses the blood—brain barrier [ 5 ]. Thus, when compared with older corticosteroids, deflazacort has a smaller suppressive effect on hypothalamic-pituitary-adrenal HPA axis, a system that modulate the physiologic response to stressors and regulate glucose and phosphocalcium metabolism and electrolyte balance.
Furthermore, given the minor impact of deflazacort on the HPA axis, a reduced risk of behavioral disorders compared to other corticosteroids has been hypothesized.
Deflazacort safety in children is a clinically relevant issue. In fact, when using corticosteroids in pediatric patients, and especially after long-term treatment, one of the most alarming adverse event is linear growth retardation; such event could be due to several mechanisms, the main of which seems to be the inhibition of Growth Hormone GH release from the pituitary gland. In children receiving long-term steroid treatment after kidney transplantation, the substitution of methylprednisolone mean dose, 0.
Deflazacort therapeutic indications include a number of pathological conditions, i. It should be emphasized that corticosteroid requirements vary from patient to patient, so the dosage should be individualized taking into account the nature of the disease and the patient's therapeutic response.
The maintenance dose should always be the minimum dose required to control the symptoms in order to minimize the risk of side effects; in any case, the dose should be reduced gradually [ 6 ]. Corticosteroids were initially introduced in clinical practice in the late '40s, when they began to be used for the treatment of rheumatoid arthritis; since then, corticosteroid therapeutic indications have expanded to various medical areas, including dermatology, rheumatology, immunology and oncology.
Systemic corticosteroids, which are used to treat several pathological conditions, are similar to endogenous steroid hormones produced by the adrenal cortex, i. Although all corticosteroids share, to varying degrees, the properties of both adrenal hormones, some of them e. The precise knowledge of the characteristics and physiological effects of corticosteroids is essential to select the most appropriate drug and to avoid problems due to its inappropriate use; therefore, the equipotency ratios between steroids is an important aspect to be considered in long-term steroid therapy.
The anti-inflammatory potency of cortisol hydrocortisone is conventionally equal to 1; hence, based on the relative potencies of various corticosteroids, it is possible to identify the equivalent doses of every single steroid. Short-acting compounds, such as hydrocortisone cortisol , show lower potencies, while intermediate-acting drugs, like prednisone and methylprednisolone, are four to five times more potent than hydrocortisone; dexamethasone, a long-acting corticosteroid, shows a potency about 25 times higher than short-acting compounds.
Corticosteroids therapeutic effects may often be associated with side effects, especially when higher doses and long-term treatment are required. To obtain the maximum benefit from therapy, it is important to prevent any potential adverse event by implementing appropriate preventive measures, as far as possible [ 19 ]. However, it should be emphasized that the risk of side effects is not only related to corticosteroid dose and duration of treatment; it also depends on the so-called Drug Therapeutic Index DTI , i.
In clinical studies, the therapeutic index can be determined by comparing the dose, or the drug concentration required to cause toxicity, with the concentration required to produce the therapeutic effects in the studied population.
However, a wider therapeutic index usually indicates a lower number and severity of side effects associated with the use of the same drug [ 1 ]. Corticosteroid doses used in clinical practice may be highly variable, depending on the disease to be treated and its severity. Deflazacort is less potent than prednisone and is usually administered at proportionately higher doses.
The potency ratio of prednisone to deflazacort is about 1: The dose equivalence of orally administered deflazacort and prednisone has been evaluated in a large US trial.
The minimum effective dose was deemed to have been reached when a minimum of two of the following events was reported: On this basis, the minimum effective dose of deflazacort was With regard to the potential of drug-induced osteoporosis, an equipotency ratio of deflazacort versus prednisolone of 1.
Consequently, at standard doses, the osteoporotic potential of deflazacort appears to be much lower than other steroids. The patients enrolled in this study were randomized in two groups: The efficacy of treatment was evaluated in each group at day 0, 90, , , and Clinical efficacy parameters included: However, although several studies have determined the equipotency ratio of deflazacort versus other corticosteroids, to the best of our knowledge, no dose-conversion table that includes also deflazacort is so far available in the literature.
Therefore, to facilitate identification of the correct dosage of this drug in clinical practice, we propose here a novel conversion table of corticosteroids doses, elaborated from literature available data i. Conversion of corticosteroid doses. Elaboration of data from [ 1 ] and [ 3 ]. The anti-inflammatory effect of corticosteroids is one of the main reasons for the use of these therapeutic agents.
Several studies on adrenal steroids with glucocorticoid activity have led to the synthesis of new molecules characterized by high anti-inflammatory potency and low incidence of side effects. Safety issues are particularly relevant in some populations on long-term therapy with corticosteroids, such as children and adolescents, in whom steroid therapy may result in growth retardation and behavioral disorders, as well as in somewhat "fragile" individuals such as politreated elderly patients.
Deflazacort is a recent synthetic glucocorticoid characterized by high efficacy and good tolerability, as demonstrated by several clinical studies that have evaluated its therapeutic efficacy and safety of use. In comparison to older corticosteroids, deflazacort shows a high anti-inflammatory and immunosuppressive activity, and a lower interference on glucose metabolism, on phosphocalcium metabolism hence, on growth and bone turnover , and on HPA axis functionality, as well as a minimal or absent sodium-retention effect.
These characteristics are favourable and suggest that deflazacort can be used safely even in pediatric and elderly populations.