Isotretinoin treatment of severe acne affects the endogenous concentration of vitamin A in sebaceous glands

Abstract

An investigation of pooled skin samples from 22 acne patients has shown that isotretinoin and its major metabolite, 4-oxo-isotretinoin, can be detected in sebaceous glands during treatment with isotretinoin (1 mg/kg/d for 4 months). The levels are less than those in the epidermis, thus excluding selective drug distribution as a prime explanation for drug function. Oral isotretinoin markedly increases retinol levels and decreases dehydroretinol levels in the skin while on therapy. The effect is more pronounced in sebaceous glands than in epidermis and dermis. The increased retinol levels probably reflect a metabolic interference with endogenous vitamin A, since isotretinoin cannot be converted into retinol in vivo. Previous studies have shown that dehydroretinol accumulates in hyperproliferative, keratinizing skin lesions and so its reduction with isotretinoin therapy may relate to a reduction in cell proliferation or to dedifferentiation. However, the precise interrelationships of these observations need further elucidation.