Identification
NameDeflazacort
Accession NumberDB11921
TypeSmall Molecule
GroupsApproved
Description

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).

Structure
Thumb
SynonymsNot Available
External IDs MDL 458 / MDL-458
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EmflazaTablet6 mg/1OralMarathon Pharmaceuticals2017-02-09Not applicableUs
EmflazaTablet36 mg/1OralMarathon Pharmaceuticals2017-02-09Not applicableUs
EmflazaTablet18 mg/1OralMarathon Pharmaceuticals2017-02-09Not applicableUs
EmflazaSuspension22.75 mg/mLOralMarathon Pharmaceuticals2017-02-09Not applicableUs
EmflazaTablet30 mg/1OralMarathon Pharmaceuticals2017-02-09Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CalcortShire
CortaxNot Available
DecortilNot Available
DeflanilNot Available
MOAIDNot Available
XalcortBeacon Pharmaceuticals Limited
ZamenNot Available
Brand mixturesNot Available
Categories
UNIIKR5YZ6AE4B
CAS number14484-47-0
WeightAverage: 441.524
Monoisotopic: 441.215137722
Chemical FormulaC25H31NO6
InChI KeyFBHSPRKOSMHSIF-GRMWVWQJSA-N
InChI
InChI=1S/C25H31NO6/c1-13-26-25(20(30)12-31-14(2)27)21(32-13)10-18-17-6-5-15-9-16(28)7-8-23(15,3)22(17)19(29)11-24(18,25)4/h7-9,17-19,21-22,29H,5-6,10-12H2,1-4H3/t17-,18-,19-,21+,22+,23-,24-,25+/m0/s1
IUPAC Name
2-[(1S,2S,4R,8S,9S,11S,12S,13R)-11-hydroxy-6,9,13-trimethyl-16-oxo-5-oxa-7-azapentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosa-6,14,17-trien-8-yl]-2-oxoethyl acetate
SMILES
[H][[email protected]@]12C[[email protected]@]3([H])[[email protected]]4([H])CCC5=CC(=O)C=C[[email protected]]5(C)[[email protected]@]4([H])[[email protected]@]([H])(O)C[[email protected]]3(C)[[email protected]@]1(N=C(C)O2)C(=O)COC(C)=O
Pharmacology
Indication

is a corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 5 years of age and older

Structured Indications
Pharmacodynamics

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.

Related Articles
Absorption

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

Not available

Protein binding

The protein binding of the active metabolite of deflazacort is about 40%.

Metabolism

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

half-life is 1.1 to 1.9 h

Clearance

Not available

Toxicity

The LD50 for the oral dose is greater than 4000 mg/kg in laboratory animals.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Mollmann H, Hochhaus G, Rohatagi S, Barth J, Derendorf H: Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone. Pharm Res. 1995 Jul;12(7):1096-100. [PubMed:7494809 ]
  2. Nayak S, Acharjya B: Deflazacort versus other glucocorticoids: a comparison. Indian J Dermatol. 2008;53(4):167-70. doi: 10.4103/0019-5154.44786. [PubMed:19882026 ]
  3. Ding W, Ding L, Li WB, Pan H, Lin HD: [Pharmacokinetics of deflazacort tablets in healthy Chinese volunteers]. Yao Xue Xue Bao. 2014 Jun;49(6):921-6. [PubMed:25212041 ]
  4. FDA label [Link]
External Links
ATC CodesH02AB13 — Deflazacort
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentDuchenne's Muscular Dystrophy (DMD)1
1CompletedBasic ScienceDuchenne's Muscular Dystrophy (DMD)1
1CompletedBasic ScienceHepatic Impairment1
1CompletedBasic ScienceImpaired Renal Function1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
2, 3CompletedTreatmentDysferlinopathy / LGMD2B / Miyoshi Myopathy1
3Active Not RecruitingTreatmentDuchenne's Muscular Dystrophy (DMD)1
Not AvailableAvailableNot AvailableDuchenne's Muscular Dystrophy (DMD)1
Not AvailableRecruitingNot AvailableIgA Nephropathy / Immunosuppressive Treatment / Proteinuria in Nephrotic Range1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
SuspensionOral22.75 mg/mL
TabletOral18 mg/1
TabletOral30 mg/1
TabletOral36 mg/1
TabletOral6 mg/1
PricesNot Available
PatentsNot Available
Properties
StateNot Available
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0175 mg/mLALOGPS
logP2.56ALOGPS
logP1.8ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)14.74ChemAxon
pKa (Strongest Basic)0.48ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area102.26 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity117.12 m3·mol-1ChemAxon
Polarizability46.79 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents20-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
SubstituentsProgestogin-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
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
substrate
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:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
substrate
General Function:
Carboxylic ester hydrolase activity
Specific Function:
Not Available
Gene Name:
CES1A1a
Uniprot ID:
Q6LAP9
Uniprot Name:
Carboxylesterase
Molecular Weight:
1908.25 Da
Drug created on October 20, 2016 15:00 / Updated on September 01, 2017 12:14