The Photoproduction of 1α,25–Dihydroxyvitamin D3in Skin

Abstract

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 1α,25–dihydroxy–7–dehydrocholesterol (1α,25(OH)₂–7–DHC) — to the corresponding hydroxylated previtamin as an alternative method of delivery of 1α,25–dihydroxyvitamin D₃ (1α,25–(OH)₂-D₃) to subjects who are deficient in the endogenous metabolite. In human volunteers and in vitamin-D-deficient rats [24³H]1α,25–(OH)₂-D₃ appeared in blood after [24³H]1α,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 1α,25–(OH)₂–7DHC combined with ultraviolet phototherapy. Delivery of equivalent doses of 1α,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. (N Engl J Med. 1980; 303:349–54.)