Isotretinoin Retinol

C15H24O 520S-9J-5) see Isotretinoin Retinol Tretinoin vinylmagnesium bromide... 

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]... 

C gH, P 603-35-0) see Acrivastine Betacarotene Calcipotriol Canthaxanthin Cefixime cis-Cefprozil Etretinate llopfost Imiquimod Isotretinoin Repaglinide Retinol Tretinoin... 

The answer is d. (Hardman, p 1575.) Isotretinoin is actually a form of high-dose vitamin A therapy Vitamin A itself or retinol (vitamin A could be used, but they have less advantageous pharmacokinetic properties. Antibiotics such as tetracyclines are used in acne, but they have little effect on the nodulocystic form... 

Not infrequently, retinol is used for mild acne, and the more active retinoids such as retinoic acid, isotretinoin, and adapalene serve for the treatment of the more severe forms. Retinol incorporated into Compritol-based SLN has been released more rapidly and to a higher extent compared with conventional vehicles and with a ) 2005 by CRC Press LLC... 

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. 

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. 

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). 

Figure 29-3. Chemical structures of important vitamin A species and the provitamin A carotenoid i-carotene. All-fra/w-fi-carolene (T) is the most important provitamin A carotenoid, which can be converted to all-fraws-retinal and then all-tram-retinol (If), which by definition is vitamin A. All-tram-retinol can be esterified with long-chain fatty acids to form retinyl ester (III), the storage form of vitaminA in the body.The active form of vitamin A in vision is 11-cts-retinal (TV).The transcriptionally active forms of vitaminA are all-tram-retinoic acid (V) and 9-cts-retinoic acid (VI). 13-cA-Retinoic acid (VII) has poor transcriptional regulatory activity but is used clinically as isotretinoin to treat skin diseases.

Retinoids for Topical Use in Acne (retinol, tretinoin, isotretinoin)... 

Retinoids. The term retinoid refers to retinol or other closely related derivatives, either natural or synthetic. Retinoids may or may not have retinol-like (vitamin A-like) activity. Retinoids affect epithelial cells by binding to receptors inside these cells, inducing alterations in the transcription of genes. Retinoids enhance the synthesis of some proteins, such as proteins that serve as receptors for certain hormones and growth factors, and reduce the synthesis of others. Some of the most commonly prescribed treatments for acne—tretinoin, isotretinoin, and adapalene—are retinoids. (See Table 1.)... 

Retinoids include natural compounds and synthetic derivatives of retinol that exhibit vitamin A activity. First-generation retinoids include retinol, tretinoin (aU-ironi-retinoic acid), isotretinoin (13-cu-retinoic acid), and alitretinoin (9-cw-retinoic acid). Second-generation retinoids, also known as aromatic retinoids, were created by alteration of the cyclic end group and include acitretin. Third-generation retinoids contain further modifications and are called arotinoids. Members of this generation include tazarotene and bexarotene. Adapalene, a derivative of naphthoic acid with retinoid-like properties, does not fit precisely into any of the three generations. 

A condition similar to vitamin A (retinol) overdosage may occur if acitretin or isotretinoin are given with vitamin A. 

Case Study 5 Isotretinoin (13-aT-retinoic acid, 22, Scheme 23.8) belongs to a family of vitamin A (retinol)-related compounds. It inhibits sebaceous gland function and keratinization and is used for the treatment of dermatological diseases such as acne. It is extremely effective in very severe and nodulocystic acne and prevents scarring. More recently, isotretinoin has been evaluated for its potential use in certain cancerous conditions. 

The first part of this chapter is devoted to the results of toxicologic, mutagenic, teratogenic, and carcinogenic studies with isotretinoin and etretinate when appropriate, a comparison with results for retinol and tretinoin (all-(rans-retinoic acid) is presented. The second part of this chapter is devoted to a description of clinical or human toxicity. 

Finally, Israili et al. (1982) reported that neither tretinoin (20 mg/kg/day), isotretinoin (80 mg/kg/day), nor retinol (23 mg/kg/day) had any effect on the incidence of squamous cell carcinoma in hairless mice exposed to UV light generated by a solar simulator. 

Retinol, tretinoin, isotretinoin, and etretinate have all been shown to be non-mutagenic or, in the case of etretinate, weakly mutagenic in the Ames test (Kamm, 1982 Hummler and Schiipbach, 1981). An unpublished study done in the laboratories of Hoffmann-La Roche has shown that isotretinoin may be weakly mutagenic in tester strain TA 100 when the assay was carried out in the presence but not in the absence of activating enzyme. 

In the sister chromatid exchange (SCE) assay, the test substance is evaluated for its ability to induce SCEs in Chinese hamster ovary cells this assay frequently incorporates an activating enzyme system as in the Ames test (Brusick, 1982). Retinol (Huang et al., 1982) and isotretinoin (Hoffmann-La Roche, unpublished) have been found to be negative in this assay. The frequency of occurrence of SCEs in human lymphocytes from subjects treated with etretinate was shown to be no different than before treatment was started (Hoffrnann-La Roche, unpublished). 

Retinoids have multiple properties in embriogenesis, growth control and differentiation of adult tissues, reproduction, and sight. In dermatology their use is well established for psoriasis, hereditary disorders of keratinization, acne, and skin aging. The most commonly used retinoids are aH-trans retinoic acid (tretinoin used topically), 13-cis retinoic acid [isotretinoin used both orally and topically), retinaldehyde/retinal and retinol [both of which are used topically). In addition there are the synthetic retinoids etretinate, acitretin, adapalene, tazarotene, etc. 

The parent compound in the vitamin A group is called sdl-trans retinol (Fig. lA) [4]. Its aldehyde and acid forms are retinal (Fig. IB) and retinoic acid (Fig. 1C). The active form of vitamin A in vision is ll-cis retinal (Fig. ID), and a therapeutically useful form (accutane, isotretinoin) is l3-cis retinoic acid (Fig. IE). Retinyl palmitate (Fig. IF) is a major storage form, and retinoyl p-glucuronide is a biologically active, relatively non-toxic water-soluble metabolite (Fig. IG). A synthetic aromatic analog (etretin, acitretin), shows therapeutic usefulness (Fig. IH). Finally, p-carotene, a major provitamin A carotenoid, is shown in Figure II. 

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