Tazarotene (AGN 190168) can be used as an adjuvant or as a monotherapy. It comes in gel and cream formulations. It is used in conjunction with steroids, calcipotriene, and phototherapy for psoriasis, and antibiotics in combination with it for acne. The tumor suppressor tazarotene (AGN 190168)-induced gene 3, which is overexpressed in psoriasis and skin cancer, has been demonstrated to be upregulated by tazarotene (AGN 190168) [1]. Tazorotene (AGN 190168) decreases the expression of two marker proteins associated in psoriasis, MRP-8 (calgranulin A) and SKALP (skin-derived antialbumin A), in human epidermal cell cultures. increased epidermal height [2].

Tazarotene (AGN 190168) is applied topically as a gel, straight into the skin. Approximately 4% to 6% of the 0.1% tazarotene (AGN 190168) gel was maintained in the stratum corneum and 2% was disseminated to the epidermis and dermis in vivo following topical application of the gel to the skin of both healthy individuals and psoriasis sufferers for 10 hours. It is intended for tazarotene (AGN 190168) to be fully and quickly converted into tazarotenic acid, which is its active metabolite. In animals, tazarotene acid has a brief duration of systemic residence and a restricted tissue distribution [3]. When administered topically, tazarotene (AGN 190168) inhibits the activity of ornithine decarboxylase (ODC) (TPA) generated by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (13-acetate) in the epidermis of hairless mice [3].

Absorption, Distribution and Excretion
Minimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.
Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.

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Metabolism / Metabolites
Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.

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Biological Half-Life
The half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Topical tazarotene has not been studied during breastfeeding. Some experts feel it should not be used on a large surface area (perhaps greater than 20% of body surface area) while nursing because of possible absorption. Others recommend that it not be used during breastfeeding because of its suspected mutagenic properties. If tazarotene is used, ensure that the infant's skin does not come into direct contact with the areas of maternal skin that have been treated and the infant does not ingest the product from the mother's skin.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
The active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).

[1]. Talpur R, et al. Efficacy and safety of topical tazarotene: a review. Expert Opin Drug Metab Toxicol. 2009 Feb;5(2):195-210.
[2]. Nagpal S, et al. Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acidreceptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ. 1996 Dec;7(12):1783-91.
[3]. Tang-Liu DD, et al. Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis. Clin Pharmacokinet. 1999 Oct;37(4):273-87.

Tazarotene is the ethyl ester of tazarotenic acid. A prodrug for tazarotenic acid, it is used for the treatment of psoriasis, acne, and sun-damaged skin. It has a role as a keratolytic drug, a prodrug and a teratogenic agent. It is a retinoid, a thiochromane, a member of pyridines, an acetylenic compound and an ethyl ester. It is functionally related to a tazarotenic acid.
Tazarotene, commonly marketed as Tazorac®, Avage®, and Zorac®, is member of the acetylenic class of retinoids. It is a prodrug that is found in topical formulations used in the treatment of various conditons, such as psoriasis, acne, and sun damaged skin (photodamage).
Tazarotene is a Retinoid.
Tazarotene is a synthetic, topical retinoid. Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. In psoriasis, tazarotene normalizes abnormal keratinocyte differentiation and reduces their hyperproliferation. (NCI04)
See also: Tazarotenic acid (has active moiety); Halobetasol propionate; tazarotene (component of); Niacinamide; tazarotene (component of) ... View More ...

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Drug Indication
Used to treat psoriasis, acne and sun damaged skin (photodamage).
FDA Label
Treatment of lamellar ichthyosis

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Mechanism of Action
Although the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors.

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Pharmacodynamics
Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.

C21H21NO2S

351.464

351.129

118292-40-3

Tazarotene-d8

5381

Light yellow to yellow solid powder

1.2±0.1 g/cm3

499.8±45.0 °C at 760 mmHg

97-98ºC

256.1±28.7 °C

0.0±1.3 mmHg at 25°C

1.625

6.22

0

4

5

25

547

0

S1C2C([H])=C([H])C(C#CC3C([H])=C([H])C(C(=O)OC([H])([H])C([H])([H])[H])=C([H])N=3)=C([H])C=2C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])[H]

OGQICQVSFDPSEI-UHFFFAOYSA-N

InChI=1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3

ethyl 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate

AGN 190168, Tazarotene, Fabior, Zorac AGN190168, AGN-190168

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~142.26 mM)
: 0.1 mg/mL (~0.28 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)