Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants

It is well known that long-term use of steroids plays a decisive role in the development of glucose intolerance and diabetes mellitus (DM). Deflazacort, an oxazoline derivative of prednisolone, has been introduced as a potential substitute for conventional steroids in order to ameliorate glucose intolerance. We initiated a randomized study of conversion from prednisone to deflazacort in kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to ascertain whether or not the switch to deflazacort would ameliorate the diabetic state. Forty-two recipients in the conversion group were compared with 40 patients on prednisone (the control group) in a prospective manner. The dose reduction of insulin or oral blood glucose-lowering agents, the adequacy of glucose control, and the development of side effects were the criteria for evaluating outcome. In the conversion group, patients were switched to deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the mean follow-up period of 13.2 months, neither graft dysfunction nor acute rejection developed in the conversion group. Improvement in blood glucose control in the conversion group was noted. When the conversion group was stratified into pre- or post-Tx DM, promising effects were clearly evident in the post-Tx DM patients. More than 50 % dose reduction of blood glucose-lowering agents was possible in 42.3 % of post-Tx DM patients. In conclusion, it was readily possible to control blood glucose better in post-Tx DM recipients without seriously affecting the immunosuppressive activity after conversion to deflazacort. Received: 20 August 1996 Received after revision: 25 November 1996 Accepted: 6 December 1996     

Deflazacort alleviate pro-inflammatory cytokines expression,oxidative stress and histopathological alterations in collagen induced arthritis in Wistar rats

ObjectivesGlucocorticoids are important and frequently used class of anti-inflammatory drugs. Deflazacort (DFZ) is a glucocorticoid and an oxazolone derivative of prednisolone. As it has high anti-inflammatory and immunosuppressive potency, we studied inhibitory effect of DFZ on mediators regulating the pro-inflammatory response and oxidative stress induced in arthritis.MethodsFemale Wistar rats were immunized intradermally by collagen type II to induce collagen induced arthritis. Arthritic rats were treated with DFZ orally (6 mg kg⁻¹ body weight) until 28 days after the onset of clinical symptoms of disease. The effect of DFZ treatment in the rats was monitored by clinical scoring, biochemical parameters, immunohistochemistry and histopathological evaluation.ResultsDeflazacort significantly decreased the level of articular elastase, nitric oxide and lipid peroxidation whereas significantly increased the activity of catalase, superoxide dismutase and glutathione. Deflazacort down-regulated expression of pro-inflammatory molecules like TNF-α and COX-2. Histopathological evaluation revealed significant reduction of synovial hyperplasia and cellular infiltration in synovial membrane in DFZ treated group as compared to the diseased group.ConclusionsThis suggests that DFZ significantly down-regulates the expression of pro-inflammatory molecules such as TNF-α and COX-2 and alleviates the oxidative stress which make it a viable therapeutic option for treatment of arthritis.     

Deflazacort induced stronger immunosuppression than expected

Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally, and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11 times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent licensed dose produced a stronger immunosuppressive effect—systemic and in brain tissue—than PDN, but induced less neuronal damage. The immunesuppressant magnitude of DFZ should be further studied in clinical settings.     

Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans

Summary The effects of two different glucocorticoids, prednisone and deflazacort, (an oxazoline derivative of prednisolone) on bone metabolism were analyzed in 10 patients with disorders that required glucocorticoid therapy. Significant elevations in blood immunoreactive parathyroid hormone, alkaline phosphatase and urinary calcium, phosphate, hydroxyproline and nephrogenous cyclic AMP were observed during prednisone therapy in addition to an increase in the exchangeable calcium pool as estimated by⁴⁷Ca-kinetic analyses. In contrast to these changes, deflazacort therapy induced minimal, and in some instances, no changes in these indices. In fact, in studies wherein prednisone therapy was followed by deflazacort alterations in bone metabolism, iPTH, and nephrogenous cAMP observed during prednisone were reversed. The data are consistent with the fact that the skeletal effects of prednisone therapy are mediated, at least in part, by increased parathyroid hormone activity, and that deflazacort is less potent in this regard.     

Corticosteroids and Tamsulosin in the Medical Expulsive Therapy for Symptomatic Distal Ureter Stones: Single Drug or Association?

OBJECTIVES: To assess the clinical role of corticosteroids in the medical expulsive therapy of symptomatic distal ureteral stones. METHODS: Between January 2004 and September 2005, 114 patients with symptomatic distal ureteral stones with a >/=5mm diameter were enrolled in this prospective study and divided into four groups based on the urologist (of four) who treated them in the emergency unit. Group A (33 patients) received tamsulosin (0.4mg daily), group B (24 patients) received deflazacort (30mg daily), group C (33 patients) received both (0.4mg tamsulosin+30mg deflazacort daily), and control group D (24 patients) received only analgesics. The treatment duration was 10 d to prevent the side-effects of prolonged corticosteroid therapy. The end points were the expulsion rate, analgesic consumption, number of ureteroscopies, and safety. RESULTS: The groups were comparable in terms of age, sex, and stone location. The stone diameter was 5.96+/-0.33mm for group A, 5.83+/-0.4mm for group B, 5.88+/-0.23mm for group C, and 5.71+/-0.5mm (p>0.05) for group D. The rates of expulsion for the four groups were 60%, 37.5%, 84.8%, and 33.3%, respectively. There was a significant difference between group C and the other groups (p<0.001). The mean analgesic consumption was 42.5+/-0.4mg for group A, 50+/-0.3mg for group B, 27.3+/-0.5mg for group C, and 81+/-0.33mg for group D, with a significant difference between group C and the other groups (p<0.001). During the treatment period, only two cases of drug side-effects related to tamsulosin (without any drop-outs) were recorded. CONCLUSION: When the medical expulsive therapy for symptomatic distal ureteral stones is considered, the use of steroids (deflazacort) proves efficient only when administered together with alpha(1)-blockers (tamsulosin). In addition, tamsulosin used on its own as a medical expulsive therapy can be considered as an alternative treatment for those patients who are not suitable for steroid therapy, as it is generally efficient.     

Clinical Equivalence between Deflazacort Oral Drops and Tablets in Active Rheumatoid Arthritis

In order to assess the clinical equivalence between deflazacort oral drops and tablets, 18 patients with active rheumatoid arthritis were enrolled in an open, controlled, randomised (‘tablets → drops’ sequence, or vice versa), two-period (21 days each) crossover trial (from tablets to drops, or vice versa). Individual dose titration of deflazacort drops or tablets was made weekly on the basis of clinical need. Primary outcome measures of efficacy were changes in the joint swelling count (JSC), erythrocyte sedimentation rate (ESR), hand-grip strength (HGS), joint pain (JP), duration of morning stiffness (MS), physician’s global evaluation and patient’s self-assessment. Sixteen patients were available by the end of the study. The formulations were equivalent with respect to HGS and improvement in duration of MS, and close to equivalence with respect to JSC and ESR decrease; the drops seemed to be more effective than tablets with respect to JP reduction. No differences between the two formulations were observed with respect to physician’s and patient’s assessment. The minimum effective dose of each preparation and the relative potency ratio were also established. Drops and tablets were found to have the same potency. Received: 14 February 1997 / Accepted: 24 October 1997     

Deflazacort in the treatment of haematologic disorders

Glucocorticoids (GCs) exert different activities that are useful for the treatment of several haematologic disorders. The synergistic effect with cytotoxic drugs is important for the therapy of lymphoprolyferative diseases. The inhibition of macrophages prevents acute haemolisys and platelets destruction in autoimmune disorders; moreover GCS are the most important agents for the management of vasculitis complicating cryoglobulinaemia.Deflazacort (DFZ) has similar immunomodulating effects to other GCs but, by contrast, DFZ produces less hypercalciuria and hyperglycaemia than prednisone and dexamethasone. As a result, the adverse effects of prolonged treatment are less with deflazacort.     

Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation

Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1 – 20 years. Methylprednisone (mean±SEM 0.17±0.01 mg/kg per day) was replaced by deflazacort (0.29±0.01 mg/kg per day) for a period of 1 – 5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6±0.5 cm/year to 5.2±0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein -3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and -II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation. Received May 13, 1996; received in revised form and accepted November 20, 1996     

Effects of prednisone and deflazacort on vertebral bone mass

Summary The effects of a 12-month therapeutic course of two different glucocorticoids, prednisone and deflazacort (an oxazoline derivative of predinisolone), on vertebral and femoral bone was analyzed by dual photon absorptiometry. The data, which reveal a significantly less bone loss with deflazacort (9.7% in 12 months) than with prednisone (21.4% in 12 months), further document the advantage of deflazacort as a glucocorticoid medication in subjects with osteopenic syndromes.     

Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica

Summary Conventional glucocorticoids exert a negative influence on calcium balance, and long-term treatment with these agents leads to osteopenia. Deflazacort is an oxazoline derivative of prednisolone with documented calcium-sparing properties when compared to prednisone on a weight basis. The purpose of the present study was to determine the relative antiinflammatory potency of deflazacort and prednisone. In a randomized, cross-over, double-blind trial, 11 patients, all suffering from polymyalgia rheumatica, and all on a stable maintenance dose of prednisone, were treated with equimolar doses of prednisone and deflazacort (i.e., weight ratio 1∶1.2) for two consecutive 2-week periods. Following deflazacort treatment, significant rises compared with initial values were seen in erythrocyte sedimentation rate (ESR), plasma fibrinogen, serum alkaline phosphatase, and general pain and tenderness. No changes were seen following prednisone treatment. Subsequently, in a similar regimen, prednisone was compared with deflazacort at a weight ratio of 1∶1.2 in 10 patients, 1∶1.5 in another 10 patients, and 1∶1.8 in still another 10 patients for purposes of dose titration. Again, significant rises were seen in ESR, plasma fibrinogen, and serum alkaline phosphatase following the lowest dose of deflazacort, whereas no changes were seen following the higher doses of deflazacort or prednisone. In conclusion, the relative antiinflammatory potency of deflazacort and prednisone lies between 0.83 and 0.66 on a weight basis (1.02 and 0.82 on a molar basis) as evaluated by clinical and biochemical parameters reflecting disease activity in polymyalgia. This disease appears to represent a sensitive, reliable and reproducible clinical model for assessment of the relative antiinflammatory potency of glucocorticoids.