Tretinoin all-trans retinoic acid

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

There are many retinol containing preparations to treat vitamin deficiency states. Retinoids are also used to treat dermatological diseases like acne, psoriasis, Darier s disease, and ichthyosis. Tretinoin, all-trans-retinoic acid, is a topical preparation while isotretinoin or 13-cis-retinoic acid, and etretinate are available for oral administration. 

Acne and psoriasis Dermatologic problems such as acne and psoriasis are effectively treated with retinoic acid or its derivatives (see Figure 28.21). Mild cases of acne, Darier disease, and skri aging are treated with topical application of tretinoin (all trans retinoic acid), as well as benzoyl peroxide and antibiotics. [Note Tretinoin is too toxic for systemic administration and is confined to topical application.] In patients with severe recalcitrant cystic acre... 

There are many types of preparations that contain retinol. Absorption is greatest for aqueous preparations, intermediate for emulsions, and slowest for oil solutions. Whereas oil-soluble preparations may lead to greater hepatic storage of the vitamin, water-miscible preparations usually provide higher concentrations in plasma. Vitamin A is available as capsules. Tretinoin (all-trans-retinoic acid Retin A) is available for topical use. Isotretinoin (13-ri.s-retinoic acid Accutane) is available for oral use, as is etretinate (Tegison). 

A potential interaction of ketoconazole with tretinoin (all-trans retinoic acid), resulting in slowed metabohsm, is probably not of importance (56). 

In commenting on Khunger et al. s [308] study, Kligman [309] notes that the pH of the tretinoin (all-trans retinoic acid) solution is approximately 6.0 and that, unlike TCA and glycolic acid, does not cause epidermal neaosis [309]. Rather, tretinoin causes a delayed peeling action due to an inflammatory response [309]. A 0.25 % tretinoin solution in 50 % ethanol and 50 % polyethylene glycol 400 has also been used [310]. 

Tretinoin (all-trans retinoic acid, ATRA) [SEDA-30, 186 SEDA-32, 301]... 

Tretinoin, also referred to ATRA, which stands for all-trans-retinoic acid, is a retinoic acid that is not cytotoxic but promotes the maturation of early promyelocytic cells and is specific to the t(15 17) cytogenetic marker. The time to peak concentrations is 1 to 2 hours after an oral dose. The elimination half-life is 21 to 51 minutes.32 These maroon-and-gold capsules are dosed at 45 mg/m2 per day divided into two doses. The most significant side effect is the retinoic acid syndrome, which may occur anywhere from the first couple of days of therapy until the end of therapy and consists of symptoms of... 

Retinoic acid (vitamin A acid), in which the alcohol group has been oxidized, shares some but not all of the actions of retinol. Retinoic acid is ineffective in restoring visual or reproductive function in certain species in which retinol is effective. Flowever, retinoic acid is very potent in promoting growth and controlling differentiation and maintenance of epithelial tissue in vitamin A-deficient animals. Indeed, all-trans-retinoic acid (tretinoin) appears to be the active form of vitamin A in all tissues except the retina, and is 10- to 100-fold more potent than retinol in various systems in vitro. Isomerization of this compound in the body yields 13-n.v-rctinoic acid (isotretinoin), which is nearly as potent as tretinoin in many of its actions on epithelial tissues but may be as much as fivefold less potent in producing the toxic symptoms of hypervitaminosis A. 

Retinoids in Dermatology 13-Qs-retinoic acid (isotretinoin, Accutane ) is used orally, and all-trans-retinoic acid (Tretinoin ) topically, for treatment of severely disfiguring cystic acne. Etretinate (the trimethoxyphenyl analog of retinoic acid) and tazarotene (a receptor-specific retinoid) are used topically for the treatment of psoriasis. They are effective in cases in which other therapy has failed, and at lower levels than are required for the control of tumor development in experimental animals, although they have heen associated with hirth defects (Section 2.5.1.1 fohnson and Chandrarama, 1999). 

Tretinoin (aU-trans-retinoic acid, ATRA) is the carboxylic acid form of vitamin A (retinol). It is one of the first-generation retinoids and has been used since the 1970s to treat acne complaints and dyskeratosis. It is important to know all about this molecule in order to obtain benefit from its actions. 

Tretinoin is a synthetic (all trans) retinoic acid. Retinol and retinaldehyde are also converted into retinoic acid in the target cell where it participates in metabolic activity. The retinoic acid penetrates the cell s nucleus, where it binds with a retinoic acid receptor (RAR). The complex formed by the retinoic acid and the RAR (RA-RAR) interferes with certain areas of DNA by modulating the expression of some genes. It appears that retinoic acid alters the regulation of the cell cycle. ... 

Retinoid and Retinoid-like Dn Used in the Treatment of Acne (Fig. 8.7) (12). The first product introduced was tretinoin, which is a topical all-trans retinoic acid. Its effectiveness may not be related to any direct retinoid activity, but attributed by its producing a complex response related to increasing... 

Guiso, G. Rambaldi, A. Dimitrova, B. Biondi, A. Caccia, S. Determination of orally administered all-trans-retinoic acid in human plasma by high-performemce liquid chromatography. J.Chromatogr.B, 1994, 656, 239—244 [all-trans-retinyl acetate (IS) extracted metabolites, isotretinoin, tretinoin LOD 10 ng/mL pharmacokinetics non-interfering allopurinol, amikacin, aracytin, ceftazidime, ciprofloxacin, doxorubicin, fluconazole, prednisone]... 

Shelley, R. Price, J.C. Jun, H.W. Cadwallader, D.E. Capomacchia, A.C. Improved and rapid high-performance liquid chromatographic assay for 13-cis-retinoic acid or all-trans-retinoic acid. J.Pharm.Sci., 1982, 71, 262-264 [rat serum extracted isotretinoin, retinol acetate, tretinoin, vitamin A pharmacokinetics LOQ 100 ng mL]... 

Retinol is available commercially in a variety of formulations, including tablets, capsules, and creams. Such products usually contain a modified form of retinol that is more easily absorbed by the body. For example, a product known as tretinoin is a synthetic form of retinol known as all-trans retinoic acid. The term all trans means that all of the double bonds in retinoic acid are located on the same side of the molecule. Products containing tretinoin are used to treat acne, pimples, wrinkles, blackheads, freckles, sun-spots, and even pre-cancerous lesions. They work by increasing the rate with which the skin sheds old cells and replaces them with new cells. 

Also note that the terms E and Z are used frequently for trans and cis, respectively. Thus all-tram retinoic acid is also known as all-E retinoic acid. Other names for aXl-trans and 13-cw (or 13-Z) retinoic acid are tretinoin and... 

Tretinoin or retinoic acid is the acid form of vitamin A. Actually it is the all-trans isomer of retinoic acid. It is an effective topical agent for acne vulgaris. Its mechanism of action is believed to be associated with increased epidermal cell turnover. Some 10% of the topically applied dose is absorbed, metabolized by the liver and excreted in the urine and bile. To be effective tretinoin should be applied in a concentration that results in mild irritation and erythema. Patients should be advised to avoid or minimize sun exposure and use a protective sun screen as animal studies have raised some concern about possible carcinogenic effects under the influence of ultraviolet radiation. There are no indications that topical tretinoin is associated with an increased risk for birth defects. 

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