Vahlquist A, Rollman O, Holland D B, Cunliffe W J
Department of Dermatology, University of Linkoping, Sweden.
J Invest Dermatol. 1990 Apr;94(4):496-8. doi: 10.1111/1523-1747.ep12874677.
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.
对22名痤疮患者的合并皮肤样本进行的一项调查显示，在用异维A酸治疗期间（1mg/kg/d，持续4个月），皮脂腺中可检测到异维A酸及其主要代谢产物4-氧代异维A酸。其水平低于表皮中的水平，因此排除了选择性药物分布作为药物作用的主要解释。口服异维A酸在治疗期间可显著提高皮肤中的视黄醇水平并降低脱氢视黄醇水平。这种作用在皮脂腺中比在表皮和真皮中更明显。视黄醇水平的升高可能反映了对内源性维生素A的代谢干扰，因为异维A酸在体内不能转化为视黄醇。先前的研究表明，脱氢视黄醇在过度增殖、角化的皮肤病变中积累，因此其在异维A酸治疗下的降低可能与细胞增殖减少或去分化有关。然而，这些观察结果的确切相互关系需要进一步阐明。
