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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
SynonymLanguageCode
(7e,9e,11e,13Z)-Retinoic acidNot AvailableNot Available
13-cis-Retinoic acidNot AvailableNot Available
13-cis-Vitamin a acidNot AvailableNot Available
13-RANot AvailableNot Available
AccutaneNot AvailableNot Available
AmnesteemNot AvailableNot Available
cis-RANot AvailableNot Available
ClaravisNot AvailableNot Available
IsotretinoinaNot AvailableNot Available
IsotretinoineNot AvailableNot Available
IsotretinoinoNot AvailableNot Available
IsotretinoinumNot AvailableNot Available
Neovitamin a acidNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Absoricacapsule10 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Absoricacapsule20 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Absoricacapsule30 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Absoricacapsule40 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Absoricacapsule25 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Absoricacapsule35 mgoralRanbaxy Laboratories Inc.2012-06-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Claruscapsule10 mgoralMylan Pharmaceuticals UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Claruscapsule40 mgoralMylan Pharmaceuticals UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Epuriscapsule10 mgoralCipher Pharmaceuticals IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Epuriscapsule20 mgoralCipher Pharmaceuticals IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Epuriscapsule30 mgoralCipher Pharmaceuticals IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Epuriscapsule40 mgoralCipher Pharmaceuticals IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Myorisancapsule, liquid filled40 mgoralPhysicians Total Care, Inc.2012-08-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Myorisancapsule, liquid filled20 mgoralPhysicians Total Care, Inc.2012-10-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zenatanecapsule, gelatin coated20 mgoralPhysicians Total Care, Inc.2014-05-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zenatanecapsule, gelatin coated40 mgoralPhysicians Total Care, Inc.2014-05-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zenatanecapsule, gelatin coated10 mgoralDr. Reddy's Laboratories Limited2013-03-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zenatanecapsule, gelatin coated20 mgoralDr. Reddy's Laboratories Limited2013-03-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zenatanecapsule, gelatin coated40 mgoralDr. Reddy's Laboratories Limited2013-03-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Myorisancapsule, liquid filled10 mgoralVersa Pharm Incorporated2012-05-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Myorisancapsule, liquid filled20 mgoralVersa Pharm Incorporated2012-05-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Myorisancapsule, liquid filled40 mgoralVersa Pharm Incorporated2012-05-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
Accutane RocheNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number4759-48-2
WeightAverage: 300.4351
Monoisotopic: 300.20893014
Chemical FormulaC20H28O2
InChI KeySHGAZHPCJJPHSC-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.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding99.9%
Metabolism
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 substrateNon-inhibitor0.8831
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral10 mg
Capsuleoral20 mg
Capsuleoral25 mg
Capsuleoral30 mg
Capsuleoral35 mg
Capsuleoral40 mg
Capsule, gelatin coatedoral10 mg
Capsule, gelatin coatedoral20 mg
Capsule, gelatin coatedoral40 mg
Capsule, liquid filledoral10 mg
Capsule, liquid filledoral20 mg
Capsule, liquid filledoral40 mg
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.
PatentsNot Available
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
SpectraMS/MS1D NMR2D NMR
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 Reference
  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
  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
  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
  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
  5. Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy] Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. Pubmed
External Links
ATC CodesD10AD04D10BA01
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (376 KB)
MSDSDownload (37.3 KB)
Interactions
Drug Interactions
Drug
CarbamazepineIsotretinoine decreases the effect of carbamazepine
DemeclocyclineIncreased risk of intracranial hypertension
DoxycyclineIncreased risk of intracranial hypertension
MethacyclineIncreased risk of intracranial hypertension
MinocyclineIncreased risk of intracranial hypertension
OxytetracyclineIncreased risk of intracranial hypertension
RolitetracyclineIncreased risk of intracranial hypertension
TetracyclineIncreased risk of intracranial hypertension
Vitamin AIsotretinoin increases the risk of vitamin A toxicity. Avoid vitamin A supplementation while taking 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

1. Retinoic acid receptor alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Retinoic acid receptor alpha P10276 Details

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
  2. Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. Pubmed
  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
  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
  5. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12