Holick M F, Uskokovic M, Henley J W, MacLaughlin J, Holick S A, Potts J T
N Engl J Med. 1980 Aug 14;303(7):349-54. doi: 10.1056/NEJM198008143030701.
Cutaneous 7-dehydrocholesterol, exposed to ultraviolet radiation, converts to previtamin D3, which in turn converts in skin to vitamin D3 and is carried into the circulation. We investigated the feasibility of the photochemical conversion in skin of hydroxylated derivatives of 7-dehydrocholesterol - such as 1 alpha, 25-dihydroxy-7-dehydrocholesterol (1 alpha, 25-(OH)2-7-DHC) - to the corresponding hydroxylated previtamin as an alternative method of delivery of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2-D3) to subjects who are deficient in the endogenous metabolite. In human volunteers and in vitamin-D-deficient rats [24-3H] 1 alpha, 25-(OH)2-D3 appeared in blood after [24-3H] 1 alpha, 25-(OH)2-7-DHC was applied to the skin and exposed to ultraviolet radiation. In anephric rats, intestinal calcium absorption and serum calcium levels were elevated after a topical dose of 1 alpha, 25-(OH)2-7-DHC combined with ultraviolet phototherapy. Delivery of equivalent doses of 1 alpha, 25-(OH)2-D3 through the skin and orally showed that there was more prolonged stimulation in intestinal calcium absorption and serum calcium elevation after cutaneous administration. The photochemical conversion of precursors may be useful in the treatment of patients with impaired vitamin-D metabolism.
皮肤中的7-脱氢胆固醇在紫外线照射下会转化为维生素D3原，维生素D3原进而在皮肤中转化为维生素D3并进入血液循环。我们研究了7-脱氢胆固醇的羟基化衍生物（如1α,25-二羟基-7-脱氢胆固醇（1α,25-(OH)2-7-DHC））在皮肤中光化学转化为相应的羟基化维生素D3原的可行性，以此作为向缺乏内源性代谢物的受试者递送1α,25-二羟基维生素D3（1α,25-(OH)2-D3）的替代方法。在人类志愿者和维生素D缺乏的大鼠中，将[24-3H]1α,25-(OH)2-7-DHC涂抹于皮肤并暴露于紫外线辐射后，血液中出现了[24-3H]1α,25-(OH)2-D3。在无肾大鼠中，局部给予1α,25-(OH)2-7-DHC并结合紫外线光疗后，肠道钙吸收和血清钙水平升高。通过皮肤和口服给予等量剂量的1α,25-(OH)2-D3表明，皮肤给药后肠道钙吸收和血清钙升高的刺激作用持续时间更长。前体的光化学转化可能对治疗维生素D代谢受损的患者有用。
