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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tazarotene--first of a new generation of receptor-selective retinoids.

Tazarotene is a topically applied retinoid that targets the skin, the site of the fundamental defect(s) in psoriasis, modulating the major causes of the disease and achieving sustained efficacy. In vitro, binding of tazarotenic acid has been demonstrated to retinoic acid receptors (RARs), the probable molecular target of retinoid action in adult human skin, but not to retinoid X receptors (RXRs). In gene activation assays, tazarotene is selective for the RAR beta and RAR gamma subtypes. This selectivity could theoretically limit undesirable effects at the receptor level. In vitro, animal and clinical evidence reveals that topical tazarotene modulates all three pathogenic factors in psoriasis: abnormal keratinocyte differentiation, hyperproliferation, and increased expression of inflammatory markers. Tazarotene is minimally absorbed systemically after topical administration. Tazarotene is rapidly metabolized by esterase metabolism to its active free-acid form, tazarotenic acid, which has a relatively short elimination half-life (1-2 h). The pharmacokinetic profile of tazarotenic acid is predictable, with no significant accumulation. In preclinical toxicity studies, high topical doses produced only reversible topical irritation, and lower doses were well tolerated. Topical doses were neither carcinogenic nor teratogenic, had no effect on fertility or general reproduction, and were not phototoxic, sensitizing, or photoallergenic. The pharmacological selectivity of tazarotene and limited systemic exposure result in minimal systemic effects, while the lesser cytotoxic effects (relative to other retinoids) result in reduced local effects.[1]


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