ro-13-6298 and Skin-Diseases

The bioavailability, plasma transport and tissue distribution of various retinoids are largely determined by their physicochemical properties; some are extremely lipidsoluble whereas others are relatively hydrophilic. Isotretinoin, a 1st generation retinoid, lacks the problematic affinity for fat. Etretinate, a 2nd generation aromatic retinoid, has been shown to accumulate in both fat tissues and in the adrenals. Etretin, the main free-acid metabolite of etretinate, is less lipophilic and is presently being tested as an alternative drug. Arotinoid ethyl ester, a 3rd generation aromatic retinoid which has as yet only undergone limited trials, is extremely potent making pharmacological evaluation difficult. The search for more potent retinoids has not so far resulted in a complete resolution of the efficacy and toxicity of the drugs.

Topics: Animals; Benzoates; Etretinate; Humans; Retinoids; Skin Diseases; Tretinoin

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: Acitretin; Administration, Oral; Benzoates; Eczema; Etretinate; Humans; Isotretinoin; Psoriasis; Retinoids; Skin Diseases; Skin Diseases, Vesiculobullous; Tretinoin

Topics: Animals; Antineoplastic Agents; Cell Division; Chemical Phenomena; Chemistry; Humans; Neoplasms; Ornithine Decarboxylase Inhibitors; Phenotype; Skin; Skin Diseases; Tretinoin; Vitamin A

The arotinoid ethyl ester Ro 13-6298 is a third generation retinoid shown to be thousand-fold more potent than etretinate (Tigason, Tegison) in animal testing and in human therapy. In an open uncontrolled trial, we treated 57 patients suffering from psoriasis (32) and various severe skin disorders (25) with daily doses ranging from 20 to 150 micrograms, during 1 to 130 weeks (mean = 12 weeks). Four patients were treated for 1 year or more. Given in micrograms per kg range, Ro 13-6298 showed a spectrum of clinical activity and mucocutaneous side effects similar to that of etretinate given in mg per kg range. One patient developed diffuse idiopathic skeletal hyperostosis after 2 years of continuous therapy. No increase in either serum triglycerides or cholesterol levels was observed, even in patients treated for 33 to 130 weeks. This might prove to be an advantage of this new retinoid. Furthermore, this series suggests that potent mucocutaneous (therapeutical and side) effects are not necessarily linked to all other signs of retinoid toxicity.

Topics: Adult; Aged; Aged, 80 and over; Benzoates; Dermatologic Agents; Female; Humans; Lipids; Liver; Male; Middle Aged; Retinoids; Skin Diseases

The effects of four retinoids, all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester ( arotinoid ) were examined on the skin of the rhino mouse. Rhino mouse skin is characterized by the presence of keratin-containing utricles attached to the epidermis, and subcutaneous cysts, both of which are derived from hair follicles. The utricles were examined in horizontal sheets of epidermis, and in vertical histologic sections. After applications of 0.1 ml of 0.1% RA, 0.1% 13-cis-RA, 0.1% aromatic retinoid, or 0.001% arotinoid in acetone to the dorsal skin for 5 days a week for 2 weeks, there was a reduction of utricle diameter to 45%, 52%, 30%, and 31% of acetone-treated controls, respectively. Histologic examination of the epidermis revealed that a dose-dependent hyperplasia and thickening of the epidermis and the stratum granulosum was induced by the retinoids when given at subtoxic doses, being most marked after arotinoid or RA. The thickness of the walls of the utricles also increased with increasing dose of retinoid, paralleling the changes in the epidermis. After doses of 0.1% RA and 0.001% arotinoid , the utricles resembled the hair follicles of hairless mice. Hyperplasia of the epidermis appears to be a primary effect of retinoids or rhino mouse skin. Hyperproliferation of the utricle wall is accompanied by a reduction in the size of the utricle lumen, preceding eventual differentiation of the utricles to normal-looking pilar units.

Topics: Animals; Benzoates; Dermatologic Agents; Etretinate; Isomerism; Isotretinoin; Keratolytic Agents; Mice; Mice, Mutant Strains; Retinoids; Skin; Skin Diseases; Tretinoin