Tretinoin

Synonyms :
(all-e)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid, 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexene-1-yl)-2,4,6,8-nonatetraenoic acid (ecl), Acide retinoique (french) (dsl), AGN 100335, All Trans Retinoic Acid, All Trans-Retinoic Acid, all-(e)-Retinoic acid, all-trans-beta-Retinoic acid, all-trans-Retinoic acid, all-trans-Tretinoin, all-trans-Vitamin a acid, all-trans-Vitamin a1 acid, ATRA, beta-Retinoic acid, Eudyna, Renova, Retin-a, RETINOIC acid, Retionic Acid, Retisol-a, Ro 1-5488, Solage, Stieva-a, trans-Retinoic acid, Tretin m, Tretinoin, Tretinoina, Trétinoïne, Tretinoine (french) (einecs), Tretinoinum, Vesanoid, Vitamin A acid, Vitinoin

Status : approved

Category

Antineoplastic Agents

Therapeutic Classification

ANTI-ACNE PREPARATIONS FOR TOPICAL USE

DERMATOLOGICALS
ANTI-ACNE PREPARATIONS
ANTI-ACNE PREPARATIONS FOR TOPICAL USE
Keratolytic Agents

Description

Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).

Used

For the the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant); For the topical treatment of acne vulgaris, flat warts and other skin conditions (psoriasis, ichthyosis congenita, icthyosis vulgaris, lamellar icthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier’s disease), and basal cell carcinomas.); For palliative therapy to improve fine wrinkling, mottled hyperpigmentation, roughness associated with photodamage.

Mechanism Of Action

Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

Dosage

Form Route Strength
Gel topical 1.200 %
Cream topical .2 mg/g
Cream topical .25 mg/g
Cream topical .5 mg/g
Cream topical 0.01 %
Cream topical 0.025 %
Cream topical 0.05 %
Cream topical 0.1 %
Cream topical 1 mg/g
Gel topical .25 mg/g
Gel topical 0.01 %
Gel topical 0.025 %
Gel topical .1 mg/g
Gel topical .4 mg/g
Gel topical .8 mg/g
Gel topical 0.04 %
Gel topical 0.1 %
Gel topical 1 mL/g
Gel topical 400 mL/g
Liquid topical .05 %
Solution topical 0.025 %
Gel topical .01 %
Gel topical 0.05 %
Gel topical 0.01 %
Gel topical 0.025 %
Cream topical .375 mg/g
Cream topical .75 mg/g
Capsule oral 10 mg
Cream topical .025 mg/g
Cream topical .05 mg/g
Cream topical .1 mg/g
Gel topical .01 mg/g
Gel topical .025 mg/g
Gel topical .04 mg/g
Gel topical .05 g/100g
Gel topical 10; .25 mg/g; mg/g
Gel topical 0.05 %
Cream topical .025 %
Cream topical .05 %
Cream topical .1 %
Gel topical .025 %
Gel topical 12; .25 mg/g; mg/g

Pharmacodynamics

Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).

Metabolism

Hepatic

Absorption

1-31% (topical)

Half Life

0.5-2 hours

Protein Binding

> 95%

Chemical Classification

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.

Retinoids

Organic compounds

Lipids and lipid-like molecules

Prenol lipids

Retinoids

Chemical Name

(all-e)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid

Brands

name Dosage form Country
Atralin gel US
Avita gel US
Avita cream US
Biacna Topical Gel gel Canada
Obagi cream US
Obagi cream US
Refissa cream US
Refissa cream US
Refissa cream US
Refissa cream US
Rejuva-a cream Canada
Renova cream US
Renova cream Canada
Renova cream US
Renova cream US
Retin-a cream US
Retin-a cream US
Retin-a gel US
Retin-a gel US
Retin-a cream US
Retin-a cream Canada
Retin-a cream Canada
Retin-a cream US
Retin-a cream US
Retin-a cream US
Retin-a cream Canada
Retin-a cream US
Retin-a cream US
Retin-a cream Canada
Retin-a gel US
Retin-a cream US
Retin-a gel Canada
Retin-a gel US
Retin-a cream US
Retin-a gel Canada
Retin-a gel US
Retin-a gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel Canada
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel US
Retin-a Micro gel Canada
Stie Vaa Sol 0.05% liquid Canada
Stieva-a Cream cream Canada
Stieva-a Cream cream Canada
Stieva-a Cream cream Canada
Stieva-a Cream cream Canada
Stieva-a Gel gel Canada
Stieva-a Gel gel Canada
Stieva-a Solution solution Canada
Stievaa Gel 0.01% gel Canada
Stievamycin Forte gel Canada
Stievamycin Mild gel Canada
Stievamycin Regular gel Canada
Tretin.x cream US
Tretin.x cream US
Tretin.x cream US
Tretin.x cream US
Tretin.x cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin gel US
Tretinoin capsule US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin gel US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin cream US
Tretinoin cream US
Tretinoin gel US
Tretinoin gel US
Tretinoin cream US
Tretinoin capsule US
Tretinoin cream US
Tretinoin cream US
Tretinoin capsule US
Tretinoin cream US
Tretinoin Cream cream US
Tretinoin Cream cream US
Tretinoin Cream cream US
Tretinoin Cream cream US
Tretinoin Gel gel US
Tretinoin Gel Microsphere gel US
Tretinoin Gel Microsphere gel US
Veltin gel US
Vesanoid capsule Canada
Vitamin A Acid 0.01% Cream cream Canada
Vitamin A Acid 0.01% Gel gel Canada
Vitamin A Acid 0.025% Cream cream Canada
Vitamin A Acid 0.025% Gel gel Canada
Vitamin A Acid 0.05% Cream cream Canada
Vitamin A Acid 0.05% Gel gel Canada
Vitamin A Acid 0.1% Cream cream Canada
Vitinoin – Crm 0.025% cream Canada
Vitinoin – Crm 0.05% cream Canada
Vitinoin – Crm 0.1% cream Canada
Vitinoin Gel – 0.025% gel Canada
Ziana gel US

Drug Drug Interactions

  •  Abiraterone  : May increase the serum concentration of CYP2C8 Substrates.
  •  Dabrafenib  : May decrease the serum concentration of CYP2C8 Substrates.
  •  Deferasirox  : May increase the serum concentration of CYP2C8 Substrates.
  •  Denosumab  : May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
  •  Leflunomide  : Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased.
  •  Menadione  : Tretinoin (Systemic) may enhance the thrombogenic effect of Antifibrinolytic Agents.
  •  Mifepristone  : May increase the serum concentration of CYP2C8 Substrates.
  •  Natalizumab  : Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
  •  Phylloquinone  : Tretinoin (Systemic) may enhance the thrombogenic effect of Antifibrinolytic Agents.
  •  Pimecrolimus  : May enhance the adverse/toxic effect of Immunosuppressants.
  •  Porfimer  : Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
  •  Roflumilast  : May enhance the immunosuppressive effect of Immunosuppressants.
  •  Sipuleucel-T  : Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
  •  Tofacitinib  : Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
  •  Tranexamic Acid  : Tretinoin (Systemic) may enhance the thrombogenic effect of Antifibrinolytic Agents.
  •  Trastuzumab  : May enhance the neutropenic effect of Immunosuppressants.
  •  Verteporfin  : Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
  •  Vitamin A  : May enhance the adverse/toxic effect of Retinoic Acid Derivatives.

Calculated Property

kind Value Source
logP 5.66 ALOGPS
logS -4.8 ALOGPS
Water Solubility 4.77e-03 g/l ALOGPS
logP 5.01 ChemAxon
IUPAC Name 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid ChemAxon
Traditional IUPAC Name isotretinoin ChemAxon
Molecular Weight 300.4351 ChemAxon
Monoisotopic Weight 300.20893014 ChemAxon
SMILES CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(O)=O ChemAxon
Molecular Formula C20H28O2 ChemAxon
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+ ChemAxon
InChIKey InChIKey=SHGAZHPCJJPHSC-YCNIQYBTSA-N ChemAxon
Polar Surface Area (PSA) 37.3 ChemAxon
Refractivity 97.79 ChemAxon
Polarizability 36.62 ChemAxon
Rotatable Bond Count 5 ChemAxon
H Bond Acceptor Count 2 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 5 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 1 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Retinoic acid receptor RXR-beta : in Human
  • Retinoic acid receptor RXR-gamma : in Human
  • Retinoic acid receptor gamma : in Human
  • Retinal dehydrogenase 1 : in Human
  • Retinoic acid-induced protein 3 : in Human
  • Nuclear receptor subfamily 0 group B member 1 : in Human
  • Retinal dehydrogenase 2 : in Human
  • Retinoic acid receptor responder protein 1 : in Human