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Identification
NameIsotretinoin
Accession NumberDB00982  (APRD00140)
TypeSmall Molecule
GroupsApproved
Description

Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used in prevention of certain skin cancers. It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. Isotretinoin binds to and activates nuclear retinoic acid receptors (RAR), thereby regulating cell proliferation and differentiation. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization.

Structure
Thumb
Synonyms
(7e,9e,11e,13Z)-Retinoic acid
13-cis-Retinoic acid
13-cis-Vitamin a acid
13-RA
Accutane
Amnesteem
cis-RA
Claravis
Isotretinoina
Isotretinoine
Isotretinoino
Isotretinoinum
Neovitamin a acid
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Absoricacapsule10 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Absoricacapsule35 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Absoricacapsule25 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Absoricacapsule40 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Absoricacapsule30 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Absoricacapsule20 mg/1oralRanbaxy Laboratories Inc.2012-06-082016-04-05Us
Accutane Rochecapsule40 mgoralHoffmann La Roche Limited1983-12-31Not applicableCanada
Accutane Rochecapsule10 mgoralHoffmann La Roche Limited1983-12-31Not applicableCanada
Claruscapsule10 mgoralMylan Pharmaceuticals Ulc2005-04-01Not applicableCanada
Claruscapsule40 mgoralMylan Pharmaceuticals Ulc2005-04-01Not applicableCanada
Epuriscapsule40 mgoralCipher Pharmaceuticals Inc2013-05-07Not applicableCanada
Epuriscapsule30 mgoralCipher Pharmaceuticals Inc2013-05-07Not applicableCanada
Epuriscapsule20 mgoralCipher Pharmaceuticals Inc2013-05-07Not applicableCanada
Epuriscapsule10 mgoralCipher Pharmaceuticals Inc2013-05-07Not applicableCanada
Isotrex Gel 0.05%gel0.05 %topicalStiefel Canada Ulc1992-12-312005-05-03Canada
Ran-isotretinoincapsule10 mgoralRanbaxy Pharmaceuticals Canada Inc.Not applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amnesteemcapsule20 mg/1oralPhysicians Total Care, Inc.2009-09-142016-04-05Us
Amnesteemcapsule10 mg/1oralMylan Pharmaceuticals Inc.2002-11-112016-04-23Us
Amnesteemcapsule10 mg/1oralPhysicians Total Care, Inc.2010-11-022016-04-05Us
Amnesteemcapsule40 mg/1oralMylan Pharmaceuticals Inc.2002-11-112016-04-23Us
Amnesteemcapsule40 mg/1oralPhysicians Total Care, Inc.2009-07-142016-04-05Us
Amnesteemcapsule20 mg/1oralMylan Pharmaceuticals Inc.2002-11-112016-04-23Us
Claraviscapsule40 mg/1oralBarr Laboratories, Inc.2003-05-092016-04-23Us
Claraviscapsule30 mg/1oralBarr Laboratories, Inc.2006-05-182016-04-23Us
Claraviscapsule40 mg/1oralPhysicians Total Care, Inc.2011-09-202016-04-05Us
Claraviscapsule20 mg/1oralBarr Laboratories, Inc.2003-05-092016-04-23Us
Claraviscapsule20 mg/1oralPhysicians Total Care, Inc.2011-09-142016-04-05Us
Claraviscapsule10 mg/1oralBarr Laboratories, Inc.2003-05-092016-04-23Us
Claraviscapsule30 mg/1oralPhysicians Total Care, Inc.2013-10-042016-04-05Us
Myorisancapsule, liquid filled40 mg/1oralVersa Pharm Incorporated2012-05-012016-04-05Us
Myorisancapsule, liquid filled20 mg/1oralPhysicians Total Care, Inc.2012-10-292016-04-05Us
Myorisancapsule, liquid filled30 mg/1oralVersa Pharm Incorporated2015-08-262016-04-05Us
Myorisancapsule, liquid filled20 mg/1oralVersa Pharm Incorporated2012-05-012016-04-05Us
Myorisancapsule, liquid filled40 mg/1oralPhysicians Total Care, Inc.2012-08-232016-04-05Us
Myorisancapsule, liquid filled10 mg/1oralVersa Pharm Incorporated2012-05-012016-04-05Us
Zenatanecapsule, gelatin coated40 mg/1oralPhysicians Total Care, Inc.2014-05-162016-04-05Us
Zenatanecapsule, gelatin coated30 mg/1oralDr. Reddy's Laboratories Limited2015-03-092016-04-05Us
Zenatanecapsule, gelatin coated20 mg/1oralPhysicians Total Care, Inc.2014-05-162016-04-05Us
Zenatanecapsule, gelatin coated40 mg/1oralDr. Reddy's Laboratories Limited2013-03-262016-04-05Us
Zenatanecapsule, gelatin coated20 mg/1oralDr. Reddy's Laboratories Limited2013-03-262016-04-05Us
Zenatanecapsule, gelatin coated10 mg/1oralDr. Reddy's Laboratories Limited2013-03-262016-04-05Us
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIEH28UP18IF
CAS number4759-48-2
WeightAverage: 300.4351
Monoisotopic: 300.20893014
Chemical FormulaC20H28O2
InChI KeyInChIKey=SHGAZHPCJJPHSC-XFYACQKRSA-N
InChI
InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14-
IUPAC Name
(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
SMILES
C\C(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(/C)=C\C(O)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassRetinoids
Direct ParentRetinoids
Alternative Parents
Substituents
  • Retinoid skeleton
  • Diterpenoid
  • Carbocyclic fatty acid
  • Medium-chain fatty acid
  • Methyl-branched fatty acid
  • Branched fatty acid
  • Fatty acyl
  • Fatty acid
  • Unsaturated fatty acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of severe recalcitrant nodular acne
PharmacodynamicsIsotretinoin, a retinoid, is indicated in the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition, means "many" as opposed to "few or several" nodules. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with Accutane, and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.
Mechanism of actionIsotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. It stabilises keratinization and prevents comedones from forming. It also reduces inflammation in moderate-severe inflammatory acne. The exact mechanism of action is unknown, however it is known that it alters DNA transcription.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding99.9%
MetabolismNot Available
Route of eliminationIsotretinoin and its metabolites are further metabolized into conjugates, which are then excreted in urine and feces. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%).
Half life17-50 hours
Clearance
  • 96 +/- 6.27 L/hr [severe recalcitrant nodular acne pediatric Patients, 12 to 15 Years]
ToxicityIsotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9311
Caco-2 permeable+0.7603
P-glycoprotein substrateNon-substrate0.6144
P-glycoprotein inhibitor INon-inhibitor0.8912
P-glycoprotein inhibitor IINon-inhibitor0.8088
Renal organic cation transporterNon-inhibitor0.8639
CYP450 2C9 substrateNon-substrate0.8221
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6025
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.8831
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9301
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9252
Ames testNon AMES toxic0.8944
CarcinogenicityNon-carcinogens0.7081
BiodegradationReady biodegradable0.5554
Rat acute toxicity2.1455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9562
hERG inhibition (predictor II)Non-inhibitor0.9538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral25 mg/1
Capsuleoral35 mg/1
Capsuleoral10 mg
Capsuleoral40 mg
Capsuleoral10 mg/1
Capsuleoral20 mg/1
Capsuleoral40 mg/1
Capsuleoral30 mg/1
Capsuleoral20 mg
Capsuleoral30 mg
Geltopical0.05 %
Capsule, liquid filledoral10 mg/1
Capsule, liquid filledoral20 mg/1
Capsule, liquid filledoral30 mg/1
Capsule, liquid filledoral40 mg/1
Capsule, gelatin coatedoral10 mg/1
Capsule, gelatin coatedoral20 mg/1
Capsule, gelatin coatedoral30 mg/1
Capsule, gelatin coatedoral40 mg/1
Prices
Unit descriptionCostUnit
Accutane 20 mg capsule23.77USD capsule
Amnesteem 40 mg capsule22.6USD capsule
Claravis 40 mg capsule22.6USD capsule
Amnesteem 20 mg capsule19.45USD capsule
Claravis 20 mg capsule18.7USD capsule
Claravis 30 mg capsule16.45USD capsule
Amnesteem 10 mg capsule16.4USD capsule
Claravis 10 mg capsule15.77USD capsule
Accutane 40 mg capsule14.88USD capsule
Accutane 10 mg capsule10.55USD capsule
Sotret 40 mg capsule10.08USD capsule
Sotret 20 mg capsule8.67USD capsule
Sotret 30 mg capsule8.44USD capsule
Sotret 10 mg capsule7.31USD capsule
Clarus 40 mg Capsule2.14USD capsule
Clarus 10 mg Capsule1.05USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7435427 No2001-09-212021-09-21Us
US8367102 No2001-09-212021-09-21Us
US8952064 No2001-09-212021-09-21Us
US9078925 No2001-09-212021-09-21Us
US9089534 No2001-09-212021-09-21Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP4.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00477 mg/mLALOGPS
logP5.66ALOGPS
logP5.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.79 m3·mol-1ChemAxon
Polarizability36.15 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000z000000-12dbd83959268dee6dbfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-jz00000000-31c9262cbbf0bad5b738View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-zo00000000-c6681587f0a9ae7a712eView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
References
Synthesis Reference

Ashok Kumar, Dharmendra Singh, Ganesh Devidas Mahale, Ragnesh Kumar Rana, Mahesh Kharade, “PROCESS FOR PREPARATION OF HIGHLY PURE ISOTRETINOIN.” U.S. Patent US20080207946, issued August 28, 2008.

US20080207946
General References
  1. Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D: Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol. 2007 Feb;63(2):196-205. [PubMed:17214828 ]
  2. Holmes SC, Bankowska U, Mackie RM: The prescription of isotretinoin to women: is every precaution taken? Br J Dermatol. 1998 Mar;138(3):450-5. [PubMed:9580798 ]
  3. Amichai B, Shemer A, Grunwald MH: Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006 Apr;54(4):644-6. [PubMed:16546586 ]
  4. Seukeran DC, Cunliffe WJ: Acne vulgaris in the elderly: the response to low-dose isotretinoin. Br J Dermatol. 1998 Jul;139(1):99-101. [PubMed:9764156 ]
  5. Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy]. Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. [PubMed:16447596 ]
External Links
ATC CodesD10AD04D10AD54D10BA01
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (376 KB)
MSDSDownload (37.3 KB)
Interactions
Drug Interactions
Drug
ChlorotrianiseneThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Isotretinoin.
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Isotretinoin.
MipomersenIsotretinoin may increase the hepatotoxic activities of Mipomersen.
NorethisteroneThe therapeutic efficacy of Norethindrone can be decreased when used in combination with Isotretinoin.
OxytetracyclineThe risk or severity of adverse effects can be increased when Oxytetracycline is combined with Isotretinoin.
PorfimerIsotretinoin may increase the photosensitizing activities of Porfimer.
VerteporfinIsotretinoin may increase the photosensitizing activities of Verteporfin.
Vitamin AThe risk or severity of adverse effects can be increased when Vitamin A is combined with Isotretinoin.
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water Do not take supplements containing Vitamin A.
  • Take with high-fat meal to increase absorption.

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
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 expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RX...
Gene Name:
RARA
Uniprot ID:
P10276
Molecular Weight:
50770.805 Da
References
  1. Dahl AR, Grossi IM, Houchens DP, Scovell LJ, Placke ME, Imondi AR, Stoner GD, De Luca LM, Wang D, Mulshine JL: Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study. Clin Cancer Res. 2000 Aug;6(8):3015-24. [PubMed:10955779 ]
  2. Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. [PubMed:16983322 ]
  3. Vu-Dac N, Gervois P, Torra IP, Fruchart JC, Kosykh V, Kooistra T, Princen HM, Dallongeville J, Staels B: Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. Contribution to the hypertriglyceridemic action of retinoids. J Clin Invest. 1998 Aug 1;102(3):625-32. [PubMed:9691099 ]
  4. Taylor LE, Bennett GD, Finnell RH: Altered gene expression in murine branchial arches following in utero exposure to retinoic acid. J Craniofac Genet Dev Biol. 1995 Jan-Mar;15(1):13-25. [PubMed:7601910 ]
  5. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed:9204085 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 01, 2016 02:28