Deflazacort is a glucocorticoid used as an anti-inflammatory and immunosuppressant. It was approved in February, 2017 by the FDA for use in treatment of Duchenne muscular dystrophy (trade name Emflaza).
|External IDs||MDL 458 / MDL-458|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 441.524 |
is a corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 5 years of age and older
Clinical studies have indicated that the average potency ratio of deflazacort to prednisolone is 0.69–0.89 and 6 mg of deflazacort is equivalent to 5 mg of prednisolone. However, the therapeutic dosage ratio has been reported to range from 1:1.2 to 1:1.5 Due to the short pharmacokinetic half-life of its active metabolite, pharmacodynamic effects of deflazacort are of shorter duration than those of methylprednisolone and prednisolone.
|Mechanism of action|
Deflazacort is a corticosteroid prodrug, whose active metabolite, 21-desDFZ, acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown.
After oral administration in the fasted state, the median Tmax with deflazacort tablets or suspension is about 1 hour (range 0.25 to 2 hours). Food Effect: Co-administration of deflazacort tablets with a high-fat meal reduced Cmax by about 30% and delayed Tmax by one hour, relative to administration under fasting conditions, but there was no effect on the overall systemic absorption as measured by AUC. The administration of deflazacort with food or crushed in applesauce did not affect the absorption and bioavailability of deflazacort. Research findings: The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2.
|Volume of distribution|
The protein binding of the active metabolite of deflazacort is about 40%.
Deflazacort is rapidly converted to the active metabolite 21-desDFZ by esterases after oral administration. 21-desDFZ is further metabolized by CYP3A4 to several other inactive metabolites.
|Route of elimination|
Urinary excretion is the predominant route of deflazacort elimination (about 68% of the dose), and the elimination is almost completed by 24 hours post dose. 21-desDFZ accounts for 18% of the eliminated drug in the urine.
half-life is 1.1 to 1.9 h
The LD50 for the oral dose is greater than 4000 mg/kg in laboratory animals.
|Pharmacogenomic Effects/ADRs||Not Available|
|Drug Interactions||Not Available|
|Food Interactions||Not Available|
|Synthesis Reference||Not Available|
|ATC Codes||H02AB13 — Deflazacort|
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Not Available|
|Experimental Properties||Not Available|
|Predicted ADMET features||Not Available|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.|
|Super Class||Lipids and lipid-like molecules|
|Class||Steroids and steroid derivatives|
|Sub Class||Pregnane steroids|
|Direct Parent||Gluco/mineralocorticoids, progestogins and derivatives|
|Alternative Parents||20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Acetate salts / Oxazolines / Imidoesters / Cyclic ketones / Cyclic alcohols and derivatives / Carboxylic acid esters / Secondary alcohols / Monocarboxylic acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Propargyl-type 1,3-dipolar organic compounds / Organic oxides / Hydrocarbon derivatives / Organonitrogen compounds|
|Substituents||Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / Hydroxysteroid / Oxosteroid / 11-beta-hydroxysteroid / 11-hydroxysteroid / Delta-1,4-steroid / Alpha-acyloxy ketone/ Cyclic alcohol / Oxazoline / Acetate salt / Carboxylic acid ester / Imido ester / Ketone / Cyclic ketone / Secondary alcohol / Monocarboxylic acid or derivatives / Propargyl-type 1,3-dipolar organic compound / Organic 1,3-dipolar compound / Carboxylic acid derivative / Oxacycle / Azacycle / Organoheterocyclic compound / Organooxygen compound / Organonitrogen compound / Alcohol / Organic oxygen compound / Hydrocarbon derivative / Organic oxide / Organic nitrogen compound / Carbonyl group / Aliphatic heteropolycyclic compound|
|Molecular Framework||Aliphatic heteropolycyclic compounds|
|External Descriptors||Not Available|
- Pharmacological action
- General Function:
- Vitamin d3 25-hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
- Gene Name:
- Uniprot ID:
- Uniprot Name:
- Cytochrome P450 3A4
- Molecular Weight:
- 57342.67 Da