Tazarotenic acid

The development of ligands selective for individual receptor subtypes relevant to a targeted disease could decrease these toxic effects thereby improving the therapeutic index. Two new arotinoids are already available for topical use in skin diseases. These are tazarotenic acid (tazarotene) and 6-[3-(l-adamanty 1)-... 

Tazarotene (Table 1) is an acetylenic third generation retinoid derivative. It is a poorly absorbed, nonisome-risable arotinoid, which is rapidly metabolized to its free carboxylic acid, tazarotenic acid, binding with high affinity to RARs, with the rank order of affinity being... 

Tazarotene is a synthetic retinoid that mediates cell differentiation and proliferation [19]. Tazarotene, a pro-drug of tazarotenic acid,has recently been proven effective as a treatment for photodamaged skin [11]. 

Tazarotene (Tazorac) is a synthetic acetylenic retinoid that is converted to its active form, tazarotenic acid, after topical application. 

Tazarotene (Tazorac) is a synthetic retinoid that is hydrolyzed to its active metabolite, tazarotenic acid, which modulates keratinocyte proliferation and differentiation. It is available as a 0.05% or 0.1% gel and cream and is applied once daily (usually in the evening) for mild to moderate plaque psoriasis. Adverse effects are dose- and frequency related and include mild to moderate pruritus, burning, stinging, and erythema. Application of the gel to eczematous skin or to more than 20% of body surface area is not recommended because this may lead to extensive systemic absorption. Tazarotene is often used with topical corticosteroids to decrease local adverse effects and increase efficacy. 

It is an acetylenic retinoid prodrug which is hydrolysed to active metabolite tazarotenic acid, binds to retinoic acid receptors resulting in modified gene expression. 

Systemically administered retinoids such as isotretinoin (1, Accutane ) have several disadvantages such as a relatively narrow therapeutic index and a variety of toxic effects including teratogenicity. Topically administered retinoids may avoid some of those drawbacks. For instance, tazarotene (2, Tazorac ) is a topical receptor-selective retenoid that normalizes differentiation and proliferation of keratinocytes. Its major metabolite, tazarotenic acid (11), binds to retinoic acid receptors (RARs) with high affinity. 

Tazarotene (2) is a prodrug. A prodrug is defined as a pharmacologically inactive chemical derivative of a drug molecule that requires a transformation within the body in order to release the active drug. In this particular case, the ethyl ester moiety is readily hydrolyzed by an esterase on skin to release the active metabolite, tazarotenic acid (11). Tazarotene (2) has a half-life of 2-18 min. and is rapidly cleared on skin. 

The pharmacokinetics and metabolism of tazarotene (2) is especially worth noting. Topical gel application provides the direct delivery of tazarotene into the skin. Ten hours after a topical application of 0.1% tazarotene gel to the skin, approximately 4-6% of the dose resides in the stratum comeum and 2% of the dose is distributed to the viable epidermis and dermis. As depicted in Scheme 3, both tazarotene (2) and tazarotenic acid (11) undergo further metabolism to their corresponding sulfoxides 12 and 13, respectively. Sulfoxides 12 and 13, in turn, are even further oxidized to sulfones 14 and 15, respectively. These very polar metabolites do not accumulate in adipose tissue, but are rapidly eliminated via both urinary and fecal pathways with a terminal half-life of approximately 18 h. A lesson learned here is that installation of a sulfide moiety promotes clearance because it is oxidized to polar metabolites that are rapidly cleared. As the consequence, the systemic exposure is minimized. Percutaneous absorption of tazarotene (2) led to a plasma concentration below 1 gg/L. The systemic... 

Tazarotene (Tazorac) is an acetylenic retinoid prodrug that is hydrolyzed to its active form by an esterase. The active metabolite, tazarotenic acid, binds to retinoic acid receptors, resulting in modified gene expression. The precise mechanism of action in psoriasis is unknown but may relate to both anti-inflammatory and antiproliferative actions. Tazarotene is absorbed percutaneously, and teratogenic systemic concentrations may be achieved if applied to more than 20% of total body surface area. Women of childbearing potential must therefore be advised of the risk prior to initiating therapy, and adequate birth control measures must be utilized while on therapy. 

Tazarotene, a prodrug and a synthetic acetylenic retinoid, is converted to its active form, tazarotenic acid, after topical application. This new-generation retinoid also selectively binds to RARs and can alter expression of genes involved in cell proliferation, cell differentiation, and inflammation." " ... 

Tazarotene, a synthetic retinoid, is a prodrug that exerts its pharmacologic activity when hydrolyzed to its active metabolite, tazarotenic acid. Like other topical retinoids, it modulates keratinocyte proliferation and differentiation." " ... 

Adapalene (6) is a naphthoic acid derivative with a methoxyphenyl adamant side-chain and is a commonly used antiacne drug [74]. Similar to the adion of tazarotene in its hydrolyzed form, tazarotenic acid, adapalene interacts seledively with RARP and RARy, and its activity on proliferation and differentiation can be blocked by a RARy antagonist [75]. In addition, adapalene has antiinflammatory potential due to its anti-API adivity [75]. Although its efficacy is similar to that of other retinoids, it has an improved therapeutic ratio due to its better tolerance (reviewed in Ref. [76]). 

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