Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Chemistry and Pharmacology of Deflazacort: A Novel Bioactive Compound for the Treatment of Duchenne Muscular Dystrophy-A Mini Review

Author(s): Mohammad Zeeshan, Arvind Kumar, Jagdish K. Sahu, Amrita Mishra and Arun K. Mishra*

Volume 15, Issue 1, 2019

Page: [41 - 44] Pages: 4

DOI: 10.2174/1573407213666171106165322

Price: $65

Abstract

Objective: Firstly, Deflazacort was synthesized in 1969 and has the structural similarity with cortisol. The present review is an attempt to summarize the updated information related to chemistry and pharmacology of Deflazacort.

Development: Deflazacort a synthetic compound synthesized by derivatization in the chemical structure of prednisolone with an aim to improve its potency. Deflazacort is under global development with Marathon Pharmaceuticals, was approved by the U.S. Food and Drug Administration in year 2017 to treat patients with Duchenne muscular dystrophy (DMD).

Chemistry and Pharmacology: DMD is one of the rare and genetic disorders with the symptoms of progressive degeneration of muscle tissue. Chemically, it is deacetylated at position 21 to produce active metabolite 21-desacetyl deflazacort (21-desDFZ), which acts through the glucocorticoid receptor. The predominant side effects are cushingoid appearance, increased appetite, upper respiratory tract infection (URTI), pollakiuria, hirsutism, and nasopharyngitis.

Conclusion: The present article summarizes the available updated information and work done so far on Deflazacort with special emphasis on its chemistry, pharmacology with detailed mechanism of action, pharmacodynamics, pharmacokinetics, metabolism and clinical trials etc.

Keywords: Duchenne muscular dystrophy, deflazacort, prednisolone, clinical trials, nephrotic syndrome, asthma, immunosuppressive agent.

Graphical Abstract

[1]
Mendell, J.R.; Shilling, C.; Leslie, N.D.; Flanigan, K.M.; al-Dahhak, R.; Gastier-Foster, J.; Kneile, K.; Dunn, D.M.; Duval, B.; Aoyagi, A.; Hamil, C.; Mahmoud, M.; Roush, K.; Bird, L.; Rankin, C.; Lilly, H.; Street, N.; Chandrasekar, R.; Weiss, R.B. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann. Neurol., 2012, 71(3), 304-313.
[2]
Ghosh, T.; Ghosh, U.; Ghosh, G.; Malik, D.; Bose, S.; Basu, U. Developing effective therapy for duchenne muscular dystrophy (DMD). Challenges and Promises. Curr. Chemical Biol., 2014, 8(3), 117-131.
[3]
Dooley, J.; Gordon, K.E.; Dodds, L.; MacSween, J. Duchenne muscular dystrophy: a 30-year population-based incidence study. Clin. Pediatr. (Phila.), 2010, 49(2), 177-179.
[4]
Ciafaloni, E.; Fox, D.J.; Pandya, S.; Westfield, C.P.; Puzhankara, S.; Romitti, P.A.; Mathews, K.D.; Miller, T.M.; Matthews, D.J.; Miller, L.A.; Cunniff, C.; Druschel, C.M.; Moxley, R.T. Delayed diagnosis in duchenne muscular dystrophy: data from the muscular dystrophy surveillance, tracking, and research network (MD STARnet). J. Pediatr., 2009, 155(3), 380-385.
[5]
Bushby, K.M.; Hill, A.; Steele, J.G. Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. Lancet, 1999, 353(9152), 557-558.
[6]
Ervasti, J.M.; Ohlendieck, K.; Kahl, S.D.; Gaver, M.G.; Campbell, K.P. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature, 1990, 345(6273), 315-319.
[7]
Zubrzycka-Gaarn, E.E.; Bulman, D.E.; Karpati, G.; Burghes, A.H.; Belfall, B.; Klamut, H.J.; Talbot, J.; Hodges, R.S.; Ray, P.N.; Worton, R.G. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature, 1988, 333(6172), 466-469.
[8]
Ameen, V.; Robson, L.G. Experimental models of duchenne muscular dystrophy: relationship with cardiovascular disease. Open Cardiovasc. Med. J., 2010, 4, 265-277.
[9]
Nayak, S.; Acharjya, B. Deflazacort versus other glucocorticoids: a comparison. Indian J. Dermatol., 2008, 53(4), 167-170.
[10]
Markham, A.; Bryson, H.M. Deflazacort. A review of its pharmacological properties and therapeutic efficacy. Drugs, 1995, 50(2), 317-333.
[11]
Ambalal, P.S.; Natvarlal, J.P. Validated spectrophotometric methods for determination of deflazacort in tablet dosage form. Asian J. Pharm. Life Sci., 2011, 1(3), 200-207.
[12]
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm540945.htm [Accessed on 8th November, 2017].
[13]
Selvadurai, M.; Meyyanathan, S.N. Determination of deflazacort in human plasma by liquid chromatography-mass spectrometry after liquid-liquid extraction and its application in human pharmacokinetics studies. Pharm. Methods, 2011, 2(2), 106-111.
[14]
Sharma, Y.; Jain, N.; Jain, H.; Jain, P.K.; Jain, A.K. Development and validation of RP-HPLC method of deflazacort for stability indicating assay. Int. J. Pharm., 2014, 4(2), 117-123.
[15]
Scremin, A.; Piazzon, M.; Silva, M.A.S.; Kuminek, G.; Correa, G.M.; Paulino, N.; Cardoso, C.G. Spectrophotometric and HPLC determination of deflazacort in pharmaceutical dosage forms. Braz. J. Pharm. Sci., 2010, 46(2), 281-287.
[16]
Luzzani, F.; Glässer, A. Differential binding in vitro to glucocorticoid receptors of deflazacort and prednisolone. Eur. J. Pharmacol., 1981, 76(4), 427-430.
[17]
Assandri, A.; Buniva, G.; Martinelli, E.; Perazzi, A.; Zerilli, L. Pharmacokinetics and metabolism of deflazacort in the rat, dog, monkey and man. Adv. Exp. Med. Biol., 1984, 171, 9-23.
[18]
Robert, C.G.; Miller, J.P.; Greenberg, C.R. Duchenne muscular dystrophy. Neurology, 2016, 87(20), 2123-2131.
[19]
Highlights of Prescribing Information. https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/208684s000,208685s000lbl.pdf [Accessed on Nov 8, 2017].
[20]
Martinelli, E.; Ferrari, P.; Ripamonti, A.; Tuan, G.; Perazzi, A.; Assandri, A. Metabolism of deflazacort in the rat, dog and man. Drug Metab. Dispos., 1979, 7(5), 335-339.

Rights & Permissions Print Cite
Article Metrics
26
3
© 2024 Bentham Science Publishers | Privacy Policy