Identification

Name
Prednicarbate
Accession Number
DB01130  (APRD01197)
Type
Small Molecule
Groups
Approved, Investigational
Description

Prednicarbate is a relatively new topical corticosteroid drug. It is similar in potency to hydrocortisone. It is used in the treatment of inflammatory skin diseases, such as atopic dermatitis. It has a favorable benefit-risk ratio, with an inflammatory action similar to that of a medium potency corticosteroid, but with a low potential to cause skin atrophy. The anti-inflammation action of corticosteroids is associated with the inhibition of the interleukin 1-alpha cytokine within keratinocytes. IL-1a is also found in fibroblasts, where it is responsible for proliferation, collagenase induction and IL-6 synthesis, which are related to skin thickness.

Structure
Thumb
Synonyms
  • Prednicarbato
External IDs
LAS-189961 / LAS189961 / S 77 0777
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DermatopOintment1 mg/1gTopicalDermik Laboratories1991-09-232015-06-30Us
DermatopOintment1 mg/1gTopicalValeant Pharmaceuticals North America2014-06-232017-04-01Us
DermatopCream1 mg/1gTopicalPhysicians Total Care, Inc.2003-11-212011-06-30Us
DermatopCream1 mg/1gTopicalDermik Laboratories1993-10-292015-09-30Us
DermatopCream1 mg/1gTopicalValeant Pharmaceuticals North America1993-10-292017-04-30Us
Dermatop Emollient CreamCream0.1 %TopicalValeant Canada Lp Valeant Canada S.E.C.2001-03-21Not applicableCanada
Dermatop OintmentOintment0.1 %TopicalValeant Canada Lp Valeant Canada S.E.C.2001-03-21Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PrednicarbateOintment1.0 mg/1gTopicalFougera Pharmaceuticals Inc.2007-03-09Not applicableUs
PrednicarbateCream1 mg/1gTopicalOceanside Pharmaceuticals1993-10-29Not applicableUs
PrednicarbateCream1 mg/1gTopicalPrasco, Laboratories2007-04-302017-04-30Us
PrednicarbateCream1 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2006-09-19Not applicableUs
International/Other Brands
Dermatop E Emollient
Categories
UNII
V901LV1K7D
CAS number
73771-04-7
Weight
Average: 488.577
Monoisotopic: 488.241018119
Chemical Formula
C27H36O8
InChI Key
FNPXMHRZILFCKX-KAJVQRHHSA-N
InChI
InChI=1S/C27H36O8/c1-5-22(31)34-15-21(30)27(35-24(32)33-6-2)12-10-19-18-8-7-16-13-17(28)9-11-25(16,3)23(18)20(29)14-26(19,27)4/h9,11,13,18-20,23,29H,5-8,10,12,14-15H2,1-4H3/t18-,19-,20-,23+,25-,26-,27-/m0/s1
IUPAC Name
2-[(1S,2R,10S,11S,14R,15S,17S)-14-[(ethoxycarbonyl)oxy]-17-hydroxy-2,15-dimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-14-yl]-2-oxoethyl propanoate
SMILES
[H][C@@]12CC[C@](OC(=O)OCC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C

Pharmacology

Indication

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

Associated Conditions
Pharmacodynamics

Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocytes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids.

Mechanism of action

In common with other topical corticosteroids, prednicarbate has anti-inflammatory, antipruritic, and vasoconstrictive properties. In general, the mechanism of the anti-inflammatory activity of topical steroids is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Absorbed systemically across the stratum corneum.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily in skin

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gupta AK, Chow M: A review of prednicarbate (Dermatop). Skin Therapy Lett. 2004 Dec-2005 Jan;9(10):5-6, 9. [PubMed:15657633]
External Links
PubChem Compound
6714002
PubChem Substance
46506799
ChemSpider
5145991
ChEBI
135791
ChEMBL
CHEMBL1200386
Therapeutic Targets Database
DAP001189
PharmGKB
PA164749394
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Prednicarbate
ATC Codes
D07AC18 — Prednicarbate
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents
FDA label
Download (130 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentPsoriasis1
2CompletedTreatmentDermatitis, Eczematous1
2CompletedTreatmentTinea Pedis1
2CompletedTreatmentCandidiasis infection1
Not AvailableCompletedTreatmentModerate to Severe Atopic Dermatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Dermik Labs
  • E. Fougera and Co.
  • Nycomed Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Physicians Total Care Inc.
  • Prasco Labs
  • Sanofi-Aventis Inc.
Dosage forms
FormRouteStrength
CreamTopical1 mg/1g
OintmentTopical1 mg/1g
CreamTopical0.1 %
OintmentTopical0.1 %
OintmentTopical1.0 mg/1g
Prices
Unit descriptionCostUnit
Prednicarbate 0.1% Ointment 60 gm Tube76.74USD tube
Dermatop 0.1% Cream 60 gm Tube75.2USD tube
Dermatop 0.1% Ointment 60 gm Tube70.06USD tube
Prednicarbate 0.1% Cream 60 gm Tube59.03USD tube
Prednicarbate 0.1% Ointment 15 gm Tube37.31USD tube
Prednicarbate 0.1% Cream 15 gm Tube24.0USD tube
Dermatop 0.1% cream1.76USD g
Prednicarbate 0.1% cream1.41USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00562 mg/mLALOGPS
logP3.08ALOGPS
logP3.83ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)14.83ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area116.2 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity127.8 m3·mol-1ChemAxon
Polarizability52.43 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.984
Caco-2 permeable-0.571
P-glycoprotein substrateSubstrate0.7928
P-glycoprotein inhibitor IInhibitor0.8358
P-glycoprotein inhibitor IINon-inhibitor0.6129
Renal organic cation transporterNon-inhibitor0.7659
CYP450 2C9 substrateNon-substrate0.8753
CYP450 2D6 substrateNon-substrate0.895
CYP450 3A4 substrateSubstrate0.7638
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9054
CYP450 2D6 inhibitorNon-inhibitor0.9032
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.841
Ames testNon AMES toxic0.9186
CarcinogenicityNon-carcinogens0.9164
BiodegradationNot ready biodegradable0.9757
Rat acute toxicity2.4426 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8758
hERG inhibition (predictor II)Non-inhibitor0.5989
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-3971000000-7e24277333421d606578

Taxonomy

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.
Kingdom
Organic compounds
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
Steroid esters / 20-oxosteroids / 3-oxo delta-1,4-steroids / 11-beta-hydroxysteroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Carbonic acid diesters / Secondary alcohols / Cyclic ketones / Cyclic alcohols and derivatives
show 4 more
Substituents
Progestogin-skeleton / Steroid ester / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Oxosteroid / Hydroxysteroid / Delta-1,4-steroid
show 17 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Boudinot FD, D'Ambrosio R, Jusko WJ: Receptor-mediated pharmacodynamics of prednisolone in the rat. J Pharmacokinet Biopharm. 1986 Oct;14(5):469-93. [PubMed:2879901]
  2. Ikonomidis I, Tzortzis S, Lekakis J, Paraskevaidis I, Andreadou I, Nikolaou M, Kaplanoglou T, Katsimbri P, Skarantavos G, Soucacos P, Kremastinos DT: Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis. Heart. 2009 Sep;95(18):1502-7. doi: 10.1136/hrt.2009.168971. Epub 2009 May 28. [PubMed:19482847]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inducer
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Litt J. (2016). Litt's Drug eruption & reaction manual (22nd ed.). CRC Press LLc.
  2. NCI/NIH [Link]
  3. University of Liverpool [Link]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 13:19