Acitretin

Identification

Summary

Acitretin is an oral retinoid used in the treatment of severe psoriasis.

Brand Names
Soriatane
Generic Name
Acitretin
DrugBank Accession Number
DB00459
Background

An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 326.4293
Monoisotopic: 326.188194698
Chemical Formula
C21H26O3
Synonyms
  • (all-E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid
  • Acitretin
  • Acitretina
  • Acitretine
  • Acitretinum
  • all-trans-3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonatetraenoic acid
  • Etretin
External IDs
  • RO 10-1670
  • RO 10-1670/000
  • RO-10-1670/000

Pharmacology

Indication

For the treatment of severe psoriasis in adults.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofKeratinization disorders••••••••••••
Management ofSevere psoriasis•••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Acitretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.

Mechanism of action

The mechanism of action of acitretin is unknown, however it is believed to work by targeting specific receptors (retinoid receptors such as RXR and RAR) in the skin which help normalize the growth cycle of skin cells.

TargetActionsOrganism
ARetinoic acid receptor RXR-alpha
agonist
Humans
ARetinoic acid receptor alpha
agonist
Humans
ARetinoic acid receptor beta
agonist
Humans
ARetinoic acid receptor gamma
agonist
Humans
ARetinoic acid receptor RXR-beta
agonist
Humans
ARetinoic acid receptor RXR-gamma
agonist
Humans
URetinol-binding protein 1
agonist
Humans
URetinoic acid receptor RXRNot Available
Absorption

Oral absorption of acitretin is optimal when given with food, and is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.

Volume of distribution

Not Available

Protein binding

Over 99.9% bound to plasma proteins, primarily albumin.

Metabolism

Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted.

Route of elimination

Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted. The chain-shortened metabolites and conjugates of acitretin and cis-acitretin are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%).

Half-life

49 hours (range 33 to 96 hours)

Clearance

Not Available

Adverse Effects
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Toxicity

Oral, rat: LD50 = >4000 mg/kg. Symptoms of overdose include headache and vertigo.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Cyproterone acetateThe therapeutic efficacy of Cyproterone acetate can be decreased when used in combination with Acitretin.
DemeclocyclineThe risk or severity of pseudotumor cerebri can be increased when Acitretin is combined with Demeclocycline.
DesogestrelThe therapeutic efficacy of Desogestrel can be decreased when used in combination with Acitretin.
DienogestThe therapeutic efficacy of Dienogest can be decreased when used in combination with Acitretin.
DiethylstilbestrolThe therapeutic efficacy of Diethylstilbestrol can be decreased when used in combination with Acitretin.
Food Interactions
  • Avoid alcohol. Women of childbearing age should avoid ingesting any alcohol during treatment and two months after discontinuation of acitretin. Alcohol intake increases the duration of risk for birth defects to beyond three years post acitretin discontinuation.
  • Take with food. Taking acitretin with the main meal of the day improves oral absorption.

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Product Images
International/Other Brands
Neotigason
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SoriataneCapsule17.5 mg/1OralStiefel Laboratories Inc2010-01-042010-04-01US flag
SoriataneCapsule17.5 mg/1OralGlaxoSmithKline Manufacturing SpA2010-01-042017-11-21US flag
SoriataneCapsule10 mg/1OralStiefel Laboratories, Inc.1996-11-012010-01-04US flag
SoriataneCapsule25 mg/1OralStiefel Laboratories Inc1996-11-012022-04-30US flag
SoriataneCapsule22.5 mg/1OralStiefel Laboratories Inc2010-01-042010-04-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AcitretinCapsule25 mg/1OralMylan Pharmaceuticals Inc.2016-03-10Not applicableUS flag
AcitretinCapsule10 mg/1OralPrasco Laboratories2013-07-192021-03-31US flag
AcitretinCapsule25 mg/1OralActavis Pharma Company2016-01-122018-05-31US flag
AcitretinCapsule10 mg/1OralSigmapharm Laboratories, LLC2015-09-16Not applicableUS flag
AcitretinCapsule10 mg/1OralActavis Pharma Company2016-02-112018-05-31US flag

Categories

ATC Codes
D05BB02 — Acitretin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Sesquiterpenoids / Styrenes / Phenoxy compounds / Methoxybenzenes / Medium-chain fatty acids / Anisoles / Methyl-branched fatty acids / Alkyl aryl ethers / Unsaturated fatty acids / Monocarboxylic acids and derivatives
show 4 more
Substituents
Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Benzenoid / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclofarsesane sesquiterpenoid / Ether
show 18 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
retinoid, alpha,beta-unsaturated monocarboxylic acid, acitretin (CHEBI:50173)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
LCH760E9T7
CAS number
55079-83-9
InChI Key
IHUNBGSDBOWDMA-AQFIFDHZSA-N
InChI
InChI=1S/C21H26O3/c1-14(8-7-9-15(2)12-21(22)23)10-11-19-16(3)13-20(24-6)18(5)17(19)4/h7-13H,1-6H3,(H,22,23)/b9-7+,11-10+,14-8+,15-12+
IUPAC Name
(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
SMILES
COC1=C(C)C(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1

References

Synthesis Reference

Yatendra Kumar, "Process for the preparation of acitretin." U.S. Patent US20040192949, issued September 30, 2004.

US20040192949
General References
Not Available
Human Metabolome Database
HMDB0014602
KEGG Drug
D02754
PubChem Compound
5284513
PubChem Substance
46509178
ChemSpider
4447573
BindingDB
50088429
RxNav
16818
ChEBI
50173
ChEMBL
CHEMBL1131
ZINC
ZINC000003798734
Therapeutic Targets Database
DAP000743
PharmGKB
PA448039
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Acitretin
FDA label
Download (530 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentPsoriasis1
4CompletedNot AvailablePsoriasis1
4CompletedTreatmentPsoriasis2
4CompletedTreatmentPsoriasis, Moderate to Severe1
4Not Yet RecruitingOtherPsoriasis Vulgaris (Plaque Psoriasis)1

Pharmacoeconomics

Manufacturers
  • Stiefel laboratories inc
Packagers
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmaceutics International Inc.
  • Stiefel Labs
Dosage Forms
FormRouteStrength
CapsuleOral22.5 mg/1
CapsuleOral
CapsuleOral10 mg
CapsuleOral25 mg
Capsule, coatedOral10 mg
CapsuleOral10.0 mg
CapsuleOral25.0 mg
CapsuleOral10 mg/1
CapsuleOral17.5 mg/1
CapsuleOral25 mg/1
Prices
Unit descriptionCostUnit
Soriatane 17.5 mg capsule30.21USD capsule
Soriatane 22.5 mg capsule30.21USD capsule
Soriatane 25 mg capsule21.71USD capsule
Soriatane 10 mg capsule13.25USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228-230 °CPhysProp
water solubility0.0729 mg/LNot Available
logP6.40SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.000478 mg/mLALOGPS
logP5.2ALOGPS
logP5.59Chemaxon
logS-5.8ALOGPS
pKa (Strongest Acidic)4.77Chemaxon
pKa (Strongest Basic)-4.8Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area46.53 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity104.17 m3·mol-1Chemaxon
Polarizability38.58 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9885
Blood Brain Barrier-0.5841
Caco-2 permeable+0.8628
P-glycoprotein substrateNon-substrate0.6057
P-glycoprotein inhibitor INon-inhibitor0.6973
P-glycoprotein inhibitor IINon-inhibitor0.9382
Renal organic cation transporterNon-inhibitor0.8899
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.8202
CYP450 3A4 substrateNon-substrate0.5108
CYP450 1A2 substrateNon-inhibitor0.6804
CYP450 2C9 inhibitorNon-inhibitor0.9239
CYP450 2D6 inhibitorNon-inhibitor0.9409
CYP450 2C19 inhibitorNon-inhibitor0.648
CYP450 3A4 inhibitorNon-inhibitor0.8768
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5923
Ames testNon AMES toxic0.8341
CarcinogenicityNon-carcinogens0.83
BiodegradationReady biodegradable0.714
Rat acute toxicity1.8804 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9216
hERG inhibition (predictor II)Non-inhibitor0.9501
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 GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-03di-1279000000-d74bbc0348cfdb3b3732
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-01t9-0592000000-92a48c620c961fdb430f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-056r-1943000000-77c18bcac662a9f6bdcb
MS/MS Spectrum - , positiveLC-MS/MSsplash10-056r-2942000000-57cdf186555912258599
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05ox-0393000000-e0dd41995d71f7f00786
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0090000000-7e026362b35382b8c39b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-015a-2290000000-7542d487bccea86a7f41
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0wmi-0980000000-a90ad8e838cb5e6bb948
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014j-0190000000-340f337aaa51d12ce4ae
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00pl-1920000000-8cc0e588bafc679eb9dc
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-217.63939
predicted
DarkChem Lite v0.1.0
[M-H]-217.96299
predicted
DarkChem Lite v0.1.0
[M-H]-196.85797
predicted
DeepCCS 1.0 (2019)
[M+H]+217.68559
predicted
DarkChem Lite v0.1.0
[M+H]+218.07359
predicted
DarkChem Lite v0.1.0
[M+H]+199.25352
predicted
DeepCCS 1.0 (2019)
[M+Na]+218.41019
predicted
DarkChem Lite v0.1.0
[M+Na]+218.08969
predicted
DarkChem Lite v0.1.0
[M+Na]+205.2307
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRA
Uniprot ID
P19793
Uniprot Name
Retinoic acid receptor RXR-alpha
Molecular Weight
50810.835 Da
References
  1. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [Article]
  2. Tian K, Norris AW, Lin CL, Li E: The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry. 1997 May 13;36(19):5669-76. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARA
Uniprot ID
P10276
Uniprot Name
Retinoic acid receptor alpha
Molecular Weight
50770.805 Da
References
  1. Saurat JH: Retinoids and psoriasis: novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol. 1999 Sep;41(3 Pt 2):S2-6. [Article]
  2. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [Article]
  3. Tian K, Norris AW, Lin CL, Li E: The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry. 1997 May 13;36(19):5669-76. [Article]
  4. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F: Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. doi: 10.1096/fj.08-121392. Epub 2009 Jan 14. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARB
Uniprot ID
P10826
Uniprot Name
Retinoic acid receptor beta
Molecular Weight
50488.63 Da
References
  1. Berggren Soderlund M, Johannesson G, Fex G: Expression of human all-trans-retinoic acid receptor beta and its ligand-binding domain in Escherichia coli. Biochem J. 1995 May 15;308 ( Pt 1):353-9. [Article]
  2. Zouboulis CC: Retinoids--which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol. 2001 Sep-Oct;14(5):303-15. [Article]
  3. Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F: Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. doi: 10.1096/fj.08-121392. Epub 2009 Jan 14. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRB
Uniprot ID
P28702
Uniprot Name
Retinoic acid receptor RXR-beta
Molecular Weight
56921.38 Da
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRG
Uniprot ID
P48443
Uniprot Name
Retinoic acid receptor RXR-gamma
Molecular Weight
50870.72 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Transporter activity
Specific Function
Intracellular transport of retinol.
Gene Name
RBP1
Uniprot ID
P09455
Uniprot Name
Retinol-binding protein 1
Molecular Weight
15850.13 Da
References
  1. Berni R, Clerici M, Malpeli G, Cleris L, Formelli F: Retinoids: in vitro interaction with retinol-binding protein and influence on plasma retinol. FASEB J. 1993 Sep;7(12):1179-84. [Article]
8. Retinoic acid receptor RXR
Kind
Group
Organism
Not Available
Pharmacological action
Unknown
References
  1. Acitretin [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Urien S, Claudepierre P, Meyer J, Brandt R, Tillement JP: Comparative binding of etretinate and acitretin to plasma proteins and erythrocytes. Biochem Pharmacol. 1992 Nov 3;44(9):1891-3. [Article]
  2. Preiss JC, Zouboulis CC, Zeitz M, Duchmann R: [Severe erythrodermic psoriasis in a patient with 22q11 deletion syndrome]. Med Klin (Munich). 2005 May 13;100(5):275-8. [Article]
  3. Carillet V, Morliere P, Maziere JC, Huppe G, Santus R, Dubertret L: In vitro interactions of the aromatic retinoids Ro 10-9359 (etretinate) and Ro 10-1670 (acitretin), its main metabolite, with human serum lipoproteins and albumin. Biochim Biophys Acta. 1990 Nov 12;1055(2):98-101. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48