Retinoid Therapy

The impact of the retinoids in clinical practice has primarily been in dermatology. When Dr Werner Bollag began his basic research and screening programme in the early 1960's, the expectation was that the retinoids would have a major impact on oncology. However, the laboratory and clinical experiences of Bollag and his colleagues in Switzerland, Stuttgen and Orfanos in Germany, led to publications on both etretinates (Tigason) and isotretinoin (Roaccutane) in the years between 1972 and 1976 in the field of dermatology. In fact the first symposium on retinoid research held in Berlin in 1981 was almost entirely dermatological. A year later a retinoid workshop in Iowa was designed to provide a forum for dermatolog ists from the USA involved in specific protocols investigating oral retinoids. In the UK, research into the retinoids began rather later than in Continental Europe or in the USA, although Tigason was first marketed here. It was felt in late 1982 that as many dermatologists had relatively little experience with these compounds it would be appropriate to hold an International Symposium on retinoid therapy in the UK. Thus on 16-18 May 1983 in London, 37 speakers from 11 countries addressed an audience of 300, aminly UK, dermatologists. The scientific organizing committee consisted of but two persons Dr William Cunliffe of Leeds General Infirmary, representing the European Society of Dermatolo gical Research, and myself from Roche Clinical Research. The Symposium was held under the auspices of the ESDR and of Roche Products Limited.

With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19 different bio transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2.

Retinoids are valuable drugs in the dermatologic armamentarium, being employed in daily clinical practice. The text provides an in-depth update on the latest thinking on pharmacology, clinical use, side effects, and follow-up of retinoid therapy in dermatology; it also addresses topics related to retinoid use in special circumstances, such as vulnerable populations, concomitant surgery, and aesthetic procedures. CONTENTS: The background of retinoids * Mechanism of action of vitamin A * Mechanism of action of topical retinoids * Mechanism of action of isotretinoin * Mechanism of action of acitretin * Mechanism of action of bexarotene * Mechanism of action of alitretinoin * Effects of retinoids at the cellular level (differentiation, apoptosis, autophagy, cell cycle regulation, and senescence) * Effects of retinoids at the systemic level * New aspects of isotretinoin teratogenicity * Mucocutaneous side effects * Ophthalmologic side effects * Musculoskeletal side effects * Neurologic side effects * Psychiatric side effects * Gastrointestinal side effects * Endocrine and metabolic side effecs * Other systemic side effects: Cardiovascular, pulmonary, otolaryngorhinologic, genitourinary, renal, and immunologic * Retinoids in acne * Retinoids in hidradenitis suppurativa/acne inversa * Retinoids in rosacea * Retinoids in hair disorders * Retinoids in psoriasis * Retinoids in keratinization disorders * Retinoids in antiaging therapy * Retinoids in other skin diseases * Retinoids in lymphoma * Retinoids in cutaneous chemoprophylaxis * Guide to good clinical practice for vulnerable populations (infancy, childhood, fertile period, elderly) * Retinoids and concomitant surgery * Retinoids and concomitant aesthetic procedures * Laboratory and clinical follow-up * Teratogenicity and registry programs * Management of vitamin A and retinoid side effects * Future and novel unexplored indications of retinoids Published in association with the Journal of Dermatological Treatment.

Recent developments with respect to the biology and clinical use of retinoids in cancer therapy and prevention are comprehensively covered by experts in this new field. Newer aspects of molecular mechanisms of retinoid effects, the cellular biology and the developmental effects of these compounds are presented together with a comprehensive description of the latest findings of retinoid pharmacology, toxicology and clinical effects in a wide range of hematological and solid malignancies.

This up-to-date reference describes how retinoids and carotenoids function in the skin and how they can be utilized to prevent and treat a wide variety of skin diseases, as well as advance biomedical research in relation to cancer treatment and immunology. Providing an in-depth update on the pharmacology, pharmacodynamics, and new applications of

The Retinoids: Biology, Biochemistry, and Disease provides an overview and synthesis of the retinoid molecules, from basic biology to mechanisms of diseases and therapy. Divided into five sections, the book covers retinoic acid signaling from biochemical, genetic, developmental, and clinical perspectives. The text is divided into five sections, the first of which examines vitamin A metabolic and enzymatic pathways. Focus then shifts to the role of retinoic acid signaling in development, and then to retinoids and physiological function. The book concludes with chapters on retinoids, disease and therapy. Comprehensive in scope and written by leading researchers in the field, The Retinoids: Biology, Biochemistry, and Disease will be an essential reference for biologists, biochemists, geneticists and developmental biologists, as well as for clinicians and pharmacists engaged in clinical research involving retinoids.