{'fraction_non_alphanumeric': 0.022102425876010783, 'fraction_numerical': 0.01293800539083558, 'mean_word_length': 5.422145328719723, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
British Society for Investigative Dermatology Annual Meeting, Birmingham, September 1989

Isotretinoin is a first line drug for systemic treatment of nodulocystic acne although its molecular mechanisms of action are poorly understood. However, since isotretinoin is closely related chemically to the naturally occurring retinoids (retinol, retinoic acid), it is possible that the drug may interfere with the endogenous metabolism of vitamin A. To study the possible interaction of isotretinoin and vitamin A at the target level we investigated 22 patients (aged 15-41 years) with severe nodulocystic acne. Drug and vitamin A levels were determined by HPLC in extracts of micro-dissected sebaceous glands obtained before and during therapy with i mg/kg per day of oral isotretinoin. After 2-4 months of treatment the isotretinoin concentrations attained in the sebaceous glands (280-440 ng/g dry weight) were 3-4 times higher than those in the surrounding dermis but somewhat lower than those in the overlying epidermis. The vitamin A content of the sebaceous glands were markedly affected by the treatment. The concentrations of retinol, the predominant form of endogenous vitamin A in the skin, increased 3-5 times as compared to pretreatment levels. In contrast, the concentrations of 3-dehydroretinol, a local metabolite of retinol, decreased to almost undetectable levels. Similar, but less pronounced, changes in the vitamin A composition were found in the epidermis. The isotretinoin-induced alterations observed suggest that the drug interacts with endogenous vitamin A metabolism in the target tissue. Since 3-dehydroretinol is known to accumulate in hyperproliferative and hyperkeratinizing skin disorders, its reduction following isotretinoin therapy may relate to the inhibition of cellular differentiation or proliferation induced by the drug.