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Green, selective and accurate high-performance liquid chromatography (HPLC) chromatographic method is presented for simultaneous separation and quantitation of the co-prescribed drugs in chemotherapy omeprazole, ondansetron and deflazacort in spiked human plasma. An isocratic HPLC separation was performed on X Bridge C18 (4.6 × 250 mm) column with 5 μm particle size using mobile phase consisting of methanol: ammonium acetate buffer pH 4 adjusted by acetic acid (60: 40, v/v). The injection volume was 20μL with UV detection wavelength at 237 nm at room temperature. Flow rate of the mobile phase was adjusted to be 2.0 ml/min. Dexamethasone was used as internal standard to correct the variation during sample pretreatment. FDA guidelines were followed to validate the developed method. Successful application of the developed method was revealed by simultaneous determination of omeprazole, ondansetron and deflazacort in spiked human plasma in ranges of 1–20, 0.1–8 and 0.2–8 μg mL−1 for omeprazole, ondansetron and deflazacort, respectively. Four greenness assessment tools were used to evaluate the greenness of the developed method and the results were accepted. This method permitted the accurate simultaneous determination of the studied drugs, thus it can be used during therapeutic drug monitoring in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background and objectives: Several recent clinical studies have indicated that vamorolone is comparable in effectiveness to glucocorticosteroids for treating Duchenne muscular dystrophy (DMD). However, there is a lack of extensive data regarding the efficacy and safety of various doses of vamorolone. We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD. Methods: We performed systematic searches of the PubMed, Embase, and Cochrane Library databases for vamorolone, glucocorticosteroids, prednisone or deflazacort in boys with DMD. We assessed statistical heterogeneity across trials based on the Newcastle Ottawa scale (NOS) tool test and I 2 values, and mean differences were pooled using the random-effects model. We used traditional meta-analysis to evaluate efficacy and safety of vamorolone 6.0 mg/ kg/d vs. vamorolone 2.0 mg/kg/d and vamorolone vs. prednisone. A network meta-analysis was applied to estimated the safety of vamorolone in comparison to glucocorticosteroids, prednisone and deflazacort. Our meta-analysis were performed using Revman 5.4 software, and our network meta-analysis were performed using Stata/MP 18.0. Results: In the meta-analysis, a total of 193 patients were analyzed across four clinical trials (97 patients receiving vamorolone 2 mg/kg per day; 96 patients receiving vamorolone 2 mg/kg per day). We observed that there were statistically significant differences in boys with DMD between vamorolone 6.0 mg/kg/d and vamorolone 2.0 mg/kg/d in TTSTANDV (MD = 0.03, 95%CI = 0.00-0.06, p = 0.04), TTRWV (MD = 0.13, 95%CI = 0.08-0.19, p < 0.01), 6MWT (MD = 24.54, 95%CI = 4.46-44.82, p = 0.02), TTCLIMBV (MD = 0.04, 95%CI = 0.01-0.06, p = 0.009), no significant difference in BMI z score (MD = 0.09, 95%CI = -0.03- 0.20, p = 0.13). Indirect comparisons derived from network meta-analysis did not show significant differences among vamorolone, glucocorticosteroids, prednisone and deflazacort in BMI z score. Conclusion: Our findings implied that boys with DMD who took vamorolone 6 mg/kg daily instead of 2 mg/kg daily may be safer and have superior motor function. However, more large sample randomized controlled trials are needed to confirm our results. Systematic Review Registration: This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916). [ABSTRACT FROM AUTHOR]

Background and Objectives: The aim of this study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling, and trismus after impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 26 healthy individuals with bilaterally impacted lower third molars. Group 1 was given a placebo (single-dose vitamin C tablet), and group 2 was given a single 30 mg dose of deflazacort 1 h prior to surgery. Pain was evaluated using the visual analogue scale for 1 week postoperatively. Oedema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann–Whitney U test was applied for group analyses. p values < 0.05 were considered statistically significant. Results: Postoperative pain scores were significantly lower in the deflazacort group at the 6th and 12th hours after surgery (p < 0.05). There were no significant differences in trismus between the groups at any time point (p > 0.05). There was less oedema in the deflazacort group on postoperative days 2 and 7, without any statistically significant difference (p > 0.05). Conclusions: A single preoperative dose of 30 mg deflazacort was found to be clinically effective in reducing pain and oedema after extraction of impacted lower third molars. [ABSTRACT FROM AUTHOR]

We studied the effect of enteral administration of the glucocorticoid deflazacort (DFC, 1.2 mg/kg per day, 28 days) on the state of skeletal muscles and tissue ultrastructure, as well as the composition of the colon microbiota in dystrophin-deficient mdx mice. DFC has been shown to reduce the intensity of degeneration/regeneration cycles in muscle fibers of mdx mice. This effect of DFC was accompanied by normalization of the size of sarcomeres of skeletal muscles of mdx mice, improvement of the ultrastructure of the subsarcolemmal population of mitochondria, and an increase in the number of organelles, as well as normalization of the number of contact interactions between the sarcoplasmic reticulum and mitochondria. In addition, DFC had a corrective effect on the colon microbiota of mdx mice, which manifested in an increase in the number of the Bifidobacterium genus microorganisms and a decrease in the level of E. coli with reduced enzymatic activity. [ABSTRACT FROM AUTHOR]

Introduction: Distal ureterolithiasis, characterized by stones in the lower ureter, poses significant challenges in clinical management. Medical expulsive therapy (MET) using Tamsulosin is a common non-invasive treatment, but its efficacy can be limited, especially for stones larger than 5 mm. Deflazacort, a corticosteroid with anti-inflammatory properties, may enhance the effectiveness of Tamsulosin by reducing ureteral inflammation and facilitating stone passage. Methods: This prospective, randomized controlled trial enrolled 80 patients with distal ureteral stones

In this study, we synthesized Zr(IV) selenophosphate/xyloglucan (ZSPT/XG) bio-nanoparticles and investigated their uses in photocatalysis and antibacterial activities. The prepared ZSPT/XG bio-nanoparticles were characterized by using X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), high-resolution transmission electron microscopy (HRTEM), Thermogravimetric analysis (TGA), Elemental analysis and UV–vis techniques. The XRD spectrum revealed the amorphous nature of the ZSPT/XG. The photocatalytic activity of ZSPT/XG bio-nanoparticles was investigated for the degradation and mineralization of deflazacort as pharmaceutical effluent from wastewaters and ZSPT/XG bio-nanoparticles demonstrated degradation of 87.04 % of deflazacort after 180 min of solar light exposure. Effect of reaction parameters of photodegradation reaction were also studied. The degradation efficiency greatly influenced by pKa value of pharmaceutical effluent and pzc value of bio-nanoparticle. The deflazacort degradation route was evaluated by Liquid Chromatography-Mass Spectrometry (LC-MS). ZSPT/XG bio-nanoparticles were tested for antibacterial activity against S. aureus and E. coli bacteria.

Aim: To examine benefits of corticosteroids for Duchenne muscular dystrophy (DMD) by age and disease progression. Methods: Data from daily steroid users (placebo-treated) were pooled from four phase 2b/3 trials in DMD. Outcomes assessed overall and among subgroups included changes from baseline to 48 weeks in six-minute walk distance (6MWD), timed function tests and North Star Ambulatory Assessment total score. Results: Among 231 patients receiving deflazacort (n = 127) or prednisone (n = 104), observed differences in 6MWD favoring deflazacort over prednisone were significant for patients with relatively older age (≥8-years-old), greater disease progression (baseline timed stand from supine ≥5 s), or longer corticosteroid use (>3 years). Conclusion: Daily deflazacort had greater benefits than daily prednisone particularly among older/more progressed patients.

BACKGROUND: Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited. OBJECTIVE: Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD. METHODS: Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models. RESULTS: This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-a antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe. [ABSTRACT FROM AUTHOR]

Use of glucocorticoid in various diseases including rheumatology and respiratory diseases is on the rise because of its prompt beneficial effects. This culminates in osteoporosis and fragility fractures. Judicious use of glucocorticoid hence calls for attention with regard to the dose schedule, route of administration and accompanying enhancing factors. Institution of proper therapeutic management as per WHO risk stratification with anabolic and/or resorptive drugs like bisphosphonates, teriparatide or denosumab is necessary to prevent the eventuality of fragility fractures. Even otherwise, knowledge of glucocorticoid, its metabolism, various dose schedules, adverse effects are areas worth discussing. [ABSTRACT FROM AUTHOR]

Deflazacort and prednisone/prednisolone are the current standard of care for patients with Duchenne muscular dystrophy (DMD) based on evidence that they improve muscle strength, improve timed motor function, delay loss of ambulation, improve pulmonary function, reduce the need for scoliosis surgery, delay onset of cardiomyopathy, and increase survival. Both have been used off-label for many years (choice dependent on patient preference, cost, and geographic location) before FDA approval of deflazacort for DMD in 2017. In this review, we compare deflazacort and prednisone/prednisolone in terms of their key pharmacological features, relative efficacy, and safety profiles in patients with DMD. Differentiating features include lipid solubility, pharmacokinetics, changes in gene expression profiles, affinity for the mineralocorticoid receptor, and impact on glucose metabolism. Evidence from randomized clinical trials, prospective studies, meta-analyses, and post-hoc analyses suggests that patients receiving deflazacort experience similar or slower rates of functional decline compared with those receiving prednisone/prednisolone. Regarding side effects, weight gain and behavior side effects appear to be greater with prednisone/prednisolone than with deflazacort, whereas bone health, growth parameters, and cataracts appear worse with deflazacort.

Background and Objectives: The aim of this study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling, and trismus after impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 26 healthy individuals with bilaterally impacted lower third molars. Group 1 was given a placebo (single-dose vitamin C tablet), and group 2 was given a single 30 mg dose of deflazacort 1 h prior to surgery. Pain was evaluated using the visual analogue scale for 1 week postoperatively. Oedema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann–Whitney U test was applied for group analyses. p values < 0.05 were considered statistically significant. Results: Postoperative pain scores were significantly lower in the deflazacort group at the 6th and 12th hours after surgery (p < 0.05). There were no significant differences in trismus between the groups at any time point (p > 0.05). There was less oedema in the deflazacort group on postoperative days 2 and 7, without any statistically significant difference (p > 0.05). Conclusions: A single preoperative dose of 30 mg deflazacort was found to be clinically effective in reducing pain and oedema after extraction of impacted lower third molars.

Asses the wound healing activity of Polyvinyl alcohol – Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. PVA-DEF nanofiber mats can be used effectively for improving wound healing. [ABSTRACT FROM AUTHOR]

Objective To investigate the motor ability and skeletal muscle pathology in mice with Duch- enne muscular dystrophy (DMD) and to explore the therapeutic effects of Deflazacort on DMD. Methods Ten - weeks-old transgenic DMD mice were selected and randomly divided into normal control group, model group and Deflazacort - treated group according to their body weights, seven in each group. The mice in all groups were weighed once a week for an experimental period of 8 weeks. At 10, 14 and 18 weeks of age, the mice were assessed for locomotor activity by hanging test, pole climbing test and grip strength test, and at 18 weeks of age, the mice were observed for changes in limb stride distance, followed by testing their walking speeds by gait test. After eutha- nasia, muscle lesions were assessed by measuring serum creatine kinase, lactate dehydrogenase, muscle pathology histology and morphological analysis. Results Compared to the DMD mice, there were no significant changes in body weight in Deflazacort -treated mice, but the suspension time was prolonged (P < 0.05), the pole climbing elapsed time reduced (P < 0.01), the forelimb grip increased (P < 0.05), and the stride distance and walking speed both increased (P < 0.01). Meanwhile, the serum creatine kinase values were lowered, and the areas of skeletal muscle inflammatory cell infiltration (P < 0.01) and fibrosis were reduced. Conclusion Deflazacort is effective in treating hypokinesia, gait bradykinesia and skeletal muscle inflammatory damage in mice with DMD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In this study we characterized disease progression over 48 weeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. METHODS: Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6 months of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48-week changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a meta-analysis. RESULTS: In the meta-analysis, deflazacort-treated patients vs prednisone/prednisolone-treated patients experienced, on average, lower declines of 28.3 meters on 6-minute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9 seconds on rise from supine [95% CI, 0.9, 4.9 seconds]; 2.3 seconds on 4-stair climb [95% CI, 0.5, 4.1 seconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). DISCUSSION: Deflazacort-treated patients experienced significantly lower functional decline over 48 weeks.

Purpose: The present study is concerned with the formulation of compression coated tablets of deflazacort. Research aimed to formulate a novel delivery system, based on chronomodulated approach for the management of rheumatoid arthritis, which is a chronic inflammatory disorder following a circadian pattern. Method: The formulation consisted of a fast disintegrating core tablet and compressed-coated layer of polymers that delayed the release of drug. The core tablets were prepared by directly compressing powder blend of drug substance, superdisintegrants, talc, magnesium stearate, and Avicel PH 101. In case of compressed-coated layer, three types of polymers (HPMC K4M, ethyl cellulose, and sodium alginate) were used to modify the release of drug from delivery system. Result: Preliminary batches were prepared to determine the effect of HPMC K4M, ethyl cellulose, and sodium alginate on lag time of the compression coated tablets. The effect of concentrations of polymers on lag time was studied for the optimization of formulation. Optimization of formulation was carried out by employing Box-Behnken Design using Design Expert 7.0. The lag time obtained from optimized batch was found to be 363.33±5.77 min. Thus, by means of an appropriate combination of excipients and suitable technique, it was possible to formulate a delivery system in which lag time followed by immediate release of drug was obtained. Conclusion: It was found that it is possible to formulate a chronotherapeutic delivery system in which the lag time and time-controlled release behavior of drug from compression-coated tablet could be modulated by varying the concentration of hydrophilic and hydrophobic polymers so that the release of drug could coordinate with the circadian pattern of disease. [ABSTRACT FROM AUTHOR]

Abstract Objectives The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5–12 years with Duchenne muscular dystrophy (DMD). Background We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003–2020) on one of five regimes: “GC naïve”, “deflazacort daily” (DD), “deflazacort intermittent” (DI), “prednisolone daily” (PD) and “prednisolone intermittent” (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90). Results The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI − 0.30, − 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation. Conclusion These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.

Aim: To examine benefits of corticosteroids for Duchenne muscular dystrophy (DMD) by age and disease progression. Methods: Data from daily steroid users (placebo-treated) were pooled from four phase 2b/3 trials in DMD. Outcomes assessed overall and among subgroups included changes from baseline to 48 weeks in six-minute walk distance (6MWD), timed function tests and North Star Ambulatory Assessment total score. Results: Among 231 patients receiving deflazacort (n = 127) or prednisone (n = 104), observed differences in 6MWD favoring deflazacort over prednisone were significant for patients with relatively older age (≥8-years-old), greater disease progression (baseline timed stand from supine ≥5 s), or longer corticosteroid use (>3 years). Conclusion: Daily deflazacort had greater benefits than daily prednisone particularly among older/more progressed patients.

INTRODUCTION: ACT DMD was a 48-week trial of ataluren for nonsense mutation Duchenne muscular dystrophy (nmDMD). Patients received corticosteroids for ≥6 months at entry and stable regimens throughout study. This post hoc analysis compares efficacy and safety for deflazacort and prednisone/prednisolone in the placebo arm. METHODS: Patients received deflazacort (n = 53) or prednisone/prednisolone (n = 61). Endpoints included change from baseline in 6-minute walk distance (6MWD), timed function tests, estimated age at loss of ambulation (extrapolated from 6MWD). RESULTS: Mean changes in 6MWD were -39.0 m (deflazacort; 95% confidence limit [CL], -68.85, -9.17) and -70.6 m (prednisone/prednisolone; 95% CL, -97.16, -44.02). Mean changes in 4-stair climb were 3.79 s (deflazacort; 95% CL, 1.54, 6.03) and 6.67 s (prednisone/prednisolone; 95% CL, 4.69, 8.64). CONCLUSIONS: This analysis, limited by its post hoc nature, suggests greater preservation of 6MWD and 4-stair climb with deflazacort vs. prednisone/prednisolone. A head-to-head comparison will better define these differences. Muscle Nerve 58: 639-645, 2018.

Duchenne muscular dystrophy (DMD) is a devastating, life-limiting neuromuscular disorder that has a global prevelance of 21.4 cases per 100,000 live male births. DMD is caused by mutations in the dystrophin gene, which is integral to muscle membrane stability. Mutations in the dystrophin gene lead to inflammation and muscle fibrosis. Current standard-of-care treatments include the use of chronic (or classic) corticosteroids, which can cause significant side effects. Vamorolone is a first-in-class dissociative steroid that acts as a partial agonist to glucocorticoid receptors but as an antagonist to mineralocorticoid receptors, leading to a more favourable side effect profile. Clinical data has shown that vamorolone has similar anti-inflammatory benefits to classic corticosteroids but an improved side effect profile. [ABSTRACT FROM AUTHOR]

The oxidative degradation pathways of deflazacort (DFL) were investigated to address the gap in understanding its degradation products, focusing on reactions with oxidative stressors such as hydrogen peroxide and 4,4'-azobis (4-cyanovaleric acid) (ACVA). Using HPLC-PDA, high-resolution mass spectrometry (HRMS), NMR and IR spectroscopy, four novel degradation products were identified and structurally characterized. Two of these products were isolated using preparative HPLC before characterization. Hydrogen peroxide led to the formation of three novel products (DP-1, DP-2, and DP-3), while ACVA resulted in a single novel product (DP-4). Mechanistic and kinetic experiments supported the proposed degradation pathways under the various oxidative stress conditions studied, revealing distinct rates of formation for the degradation products during the time-course study. The identification and detailed structural elucidation of these degradation products provide critical insights into the chemical stability and potential reactivity of DFL under oxidative stress. These findings underscore the importance of comprehensive stability testing for ensuring drug safety and efficacy, and offer valuable data for future research on the toxicity and pharmacological impact of DFL degradation products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration and weakness, caused by mutations in the dystrophin gene. DMD has effects in early age with significantly shortened lifespan and deteriorated quality of life in the second decade, creating an urgent need to develop better therapeutic options. Corticosteroid medication therapy is an integral tool for the management of DMD and several therapeutic options have been recently approved for use., Areas Covered: A comprehensive literature search was completed to examine efficacy and safety profiles of the three corticosteroid medications available for use in DMD patients. The review presents information about the three agents through clinical trials, significant preclinical trials, and comparative studies., Expert Opinion: Managing DMD takes a multidisciplinary approach, although long-term corticosteroid therapy remains a significant therapeutic tool. Based on the available published studies, unequivocal comparison between the benefits of the three medications cannot yet be made. When selecting a medication for a patient, the decision-making process will most likely rely on the minor differences in the adverse effect profiles. Whichever medication is utilized will surely be a part of a larger regimen that includes other novel therapeutic agents.

Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments.

US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD) and recommended the dosage of 0.9 mg/kg/d for patients aged ≥5years. However, data assessing the minimal efficacious dose and need of dose-titration based on age or disease severity is limited. To determine whether deflazacort 0.45 mg/kg/d (proposed lower dosage) is non-inferior to 0.9 mg/kg/d among newly diagnosed patients with DMD. A double-blinded, non-inferiority, randomized trial, conducted between December 2018 and July 2020. Newly diagnosed patient aged 5–15 years with genetic or muscle biopsy confirmed DMD and baseline 6-min walk distance (6MWD) > 150 m were screened. Patients were randomly assigned (1:1), stratified to prespecified subgroups by age (≤7years and >7years), and baseline 6MWD (≤350 m and >350 m), to receive either 0.45 mg/kg/d or 0.9 mg/kg/d regimens. The primary endpoint was the change in 6MWD, from baseline to week-24 of intervention. The trial was powered with a predefined, non-inferiority margin of 30 m. The analyses were by modified intention-to-treat (mITT). A total of 97 patients were enrolled, 40 receiving 0.45 mg/kg/d and 45 receiving 0.9 mg/kg/d deflazacort comprised of mITT population. For primary endpoint analysis the mean (SD) change in 6MWD from baseline to week-24 was 9.7 m (41.5) in deflazacort 0.45 mg/kg/d, and 34.7 m (43.5) for 0.9 mg/kg/d. The mean difference in change in 6MWD across the group was 24.8 m (95% CI 6.7 to 43, p value 0.008). The mean difference in change in 6MWD in the subgroups of boys ≤7 years of age was 21.8 m (95% CI -0.82, 44.5, p = 0.059), with baseline 6MWD of >350 m was 19.9 m (95% CI -2.4, 42.4; p = 0.08). The incidence of combined moderate to severe treatment-related adverse events was significant in the 0.9 mg/kg/d group by week 24 (odds ratio 0.36 [95% CI, 0.14 to 0.89], p = 0.03). The efficacy of proposed low dose deflazacort in comparison to the standard dose did not meet the prespecified criteria for non-inferiority. The low dose deflazacort was non-inferior in subgroup of patients with age ≤7 years and baseline 6MWD of >350 m. Clinical Trial Registry-India Identifier: CTRI/2019/02/017388. • US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD). • Data assessing dose response and minimal efficacious dose is limited. • Efficacy of low dose deflazacort (0.45 mg/kg/day) is inferior to standard recommended (0.9 mg/kg/day) dose measured by change in 6-min walk distance (6MWD) from baseline to week 24. • The proposed low dose deflazacort was non-inferior to standard dose in a subgroup of boys with age <7 years and baseline 6MWD >350 m. • Combined moderate to severe side-effects were significantly less with low dose deflazacort. [ABSTRACT FROM AUTHOR]

Adel A Ali, Amira H Hassan, Essam M Eissa, Heba M Aboud Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptCorrespondence: Heba M AboudDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptTel +20822162135Fax +20822162136Email heba.aboud@pharm.bsu.edu.egPurpose: The aim of the present study was to develop deflazacort (DFZ) ultra-elastic nanovesicles (UENVs) loaded gel for topical administration to evade gastrointestinal adverse impacts accompanying DFZ oral therapy.Methods: UENVs were elaborated according to D-optimal mixture design employing different edge activators as Span-60, Tween-85 and sodium cholate which were incorporated into the nanovesicles to improve the deformability of vesicles bilayer. DFZ-UENVs were formulated by thin-film hydration technique followed by characterization for different parameters including entrapment efficiency (%EE), particle size, in vitro release and ex vivo permeation studies. The composition of the optimized DFZ-UENV formulation was found to be DFZ (10 mg), Span-60 (30 mg), Tween-85 (30 mg), sodium cholate (3.93 mg), L-α phosphatidylcholine (60 mg) and cholesterol (30 mg). The optimum formulation was incorporated into hydrogel base then characterized in terms of physical parameters, in vitro drug release, ex vivo permeation study and pharmacodynamics evaluation. Finally, pharmacokinetic study in rabbits was performed via transdermal application of UENVs gel in comparison to oral drug.Results: The optimum UENVs formulation exhibited %EE of 74.77± 1.33, vesicle diameter of 219.64± 2.52 nm, 68.88± 1.64% of DFZ released after 12 h and zeta potential of − 55.57± 1.04 mV. The current work divulged successful augmentation of the bioavailability of DFZ optimum formulation by about 1.37-fold and drug release retardation compared to oral drug tablets besides significant depression of edema, cellular inflammation and capillary congestion in carrageenan-induced rat paw edema model.Conclusion: The transdermal DFZ-UENVs can achieve boosted bioavailability and may be suggested as an auspicious non-invasive alternative platform for oral route.Keywords: deflazacort, ultra-elastic nanovesicles, D-optimal design, pharmacodynamics, pharmacokinetics

Objectives: The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD).Background: We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003-2020) on one of five regimes: "GC naïve", "deflazacort daily" (DD), "deflazacort intermittent" (DI), "prednisolone daily" (PD) and "prednisolone intermittent" (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90).Results: The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI - 0.30, - 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation.Conclusion: These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC. [ABSTRACT FROM AUTHOR]

Abstract Background Extracorporeal shock wave lithotripsy (ESWL) is the treatment of choice for upper tract calculi of moderate size. After ESWL, various factors affect the passage of small fragments through ureter like fragment’s size and location. To facilitate fragment passage, a lot of medications have been tried and few have stood the test of the time. In this prospective study, we evaluated the role of Tamsulosin with or without Deflazacort versus no treatment after ESWL for ureteric and renal stones in terms of requirement of the number of ESWL sessions, stone clearance rate, stone expulsion time and analgesia requirements. Results Patients presenting between age-groups of 18–70 years with solitary renal/ureteric calculus of size between 6 and 15 mm in major axis with Hounsfield unit less than 1000 were recruited in one of the three groups (A, B and C) randomly. Patients in Group A were prescribed Tamsulosin (0.4 mg once daily) with Deflazacort (30 mg once daily), Group B were given Tamsulosin (0.4 mg once daily), and Group C received no treatment (analgesics SOS and hydration therapy) after undergoing ESWL. Two hundred and twenty-five patients were recruited in Group A, and 240 patients were recruited in Group B and Group C each. There was an insignificant difference for required mean ESWL sessions and stone clearance rate between three groups. There was an early clearance of stone fragments in Group A than in Groups B and C, and it was statistically significant between Group A and Group C, specifically in the subgroup of stone size 10.1–15 mm. The requirement of mean analgesic tablets difference was significant between Groups A and C. Conclusions Tamsulosin with Deflazacort decreases the number of required ESWL sessions and improves complete stone clearance, but the difference is not significant. There were significant improvement in facilitating early stone clearance and decrease in requirement of mean analgesic tablets after ESWL with Tamsulosin and Deflazacort. Thus, Tamsulosin with Deflazacort can be used safely to facilitate stone clearance without increased complication rate.

Background and Objectives: Several recent clinical studies have indicated that vamorolone is comparable in effectiveness to glucocorticosteroids for treating Duchenne muscular dystrophy (DMD). However, there is a lack of extensive data regarding the efficacy and safety of various doses of vamorolone. We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD., Methods: We performed systematic searches of the PubMed, Embase, and Cochrane Library databases for vamorolone, glucocorticosteroids, prednisone or deflazacort in boys with DMD. We assessed statistical heterogeneity across trials based on the Newcastle Ottawa scale (NOS) tool test and I 2 values, and mean differences were pooled using the random-effects model. We used traditional meta-analysis to evaluate efficacy and safety of vamorolone 6.0 mg/kg/d vs. vamorolone 2.0 mg/kg/d and vamorolone vs. prednisone. A network meta-analysis was applied to estimated the safety of vamorolone in comparison to glucocorticosteroids, prednisone and deflazacort. Our meta-analysis were performed using Revman 5.4 software, and our network meta-analysis were performed using Stata/MP 18.0., Results: In the meta-analysis, a total of 193 patients were analyzed across four clinical trials (97 patients receiving vamorolone 2 mg/kg per day; 96 patients receiving vamorolone 2 mg/kg per day). We observed that there were statistically significant differences in boys with DMD between vamorolone 6.0 mg/kg/d and vamorolone 2.0 mg/kg/d in TTSTANDV (MD = 0.03, 95%CI = 0.00-0.06, p  = 0.04), TTRWV (MD = 0.13, 95%CI = 0.08-0.19, p  < 0.01), 6MWT (MD = 24.54, 95%CI = 4.46-44.82, p  = 0.02), TTCLIMBV (MD = 0.04, 95%CI = 0.01-0.06, p  = 0.009), no significant difference in BMI z score (MD = 0.09, 95%CI = -0.03-0.20, p  = 0.13). Indirect comparisons derived from network meta-analysis did not show significant differences among vamorolone, glucocorticosteroids, prednisone and deflazacort in BMI z score., Conclusion: Our findings implied that boys with DMD who took vamorolone 6 mg/kg daily instead of 2 mg/kg daily may be safer and have superior motor function. However, more large sample randomized controlled trials are needed to confirm our results., Systematic Review Registration: This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zeng, Jiao, He, Li, Guo and Song.)

Background: Delayed puberty is thought to be common in boys with Duchenne muscular dystrophy (DMD) treated with long term oral glucocorticoid. This study aims to report the frequency of delayed puberty in DMD from examination by a paediatric endocrinologist alongside detailed endocrine investigations., Methods: All boys with DMD aged at least 14 years in January 2022 known to the paediatric neuromuscular service (2016-2022) were included in this study. Delayed puberty was defined based on testicular volume and genital staging in comparison to published puberty nomogram., Results: Twenty-four out of 37 boys (65%) had evidence of delayed puberty, 23/24 (96%) of those with delayed puberty were on glucocorticoid therapy all of whom were on daily glucocorticoid. On the other hand, 7/13 (54%) of those with normal timing of puberty were on glucocorticoid; 2/7 (29%) were on the intermittent regimen. Of those who were on daily glucocorticoid therapy at the time of assessment of puberty, 23/28 (82%) had evidence of delayed puberty. In boys with delayed puberty, endocrine investigations showed low luteinizing hormone (LH) with undetectable testosterone levels, a pre-pubertal response with lutenizing hormone releasing hormone test and sub-optimal testosterone levels with prolonged human chorionic gonadotropin stimulation., Conclusion: The frequency of delayed puberty in boys with DMD was 65%. Eighty-two percent of adolescent boys with DMD on daily glucocorticoid had evidence of delayed puberty. Biochemical investigations point to functional central hypogonadism in these adolescents. Our data supports the routine monitoring of puberty in boys with DMD.

The aim and objective of the present work has been to develop new simple, sensitive and validated RP-HPLC method for the estimation of drugs in marketed formulation. Validation of developed Analytical methods according to ICH guidelines. Stress study was performed on Deflazacort and was found that it degrade sufficiently in acidic, alkaline and oxidative condition but less degradation was found in thermal and photolytic oxidation the % of degradation of active constituents was found to be 16.64%, 10.25 %and 8.67% respectively. The analysis was carried out on waters HPLC. It has 715 binary pumps, Rheodyne injector with a 20-microlitre loop, U.V. Vis. Detector, Thermo C-18 column (4.6 x 250mm, 5µ particle size) with data ace software. and the mobile Phase composition was water -methanol ratio 80:20 flow rate 1ml/min, methanol-water ratio 70:30 flow rate 1.2 ml/min, acetonitrile-water ratio 40:60 flow rate 1.2ml/min and methanol - acetonitrile ratio 50:50 fl0w rate 1ml/min at room temperature and most suitable. The sample injection volume was 20 uL, and eluents of the isocratic elution mode were monitored at 241nm. The retention time was 5.25 min. The method was linear in the concentration range of 5-25 ug/ml with an 16.14 r2=0.999. The LOD and LOQ were found to 0.82ug/mL and 2.41ug/mL of Deflazacort. [ABSTRACT FROM AUTHOR]