Physiological and pharmacological aspects of 24,25-dihydroxycholecalciferol in man.
The present study describes the response to small oral doses (1--10 microgram/day) of 24,25-DHCC in man. Contrary to expectation, 24,25-DHCC was as potent as 1,25-DHCC in increasing intestinal absorption of calcium both in normal persons and in patients with a variety of disorders of calcium metabolism. Despite this increase in intestinal absorption, plasma and urine calcium did not increase after 24,25-DHCC as they did after 1,25-DHCC. Metabolic balance studies showed calcium balances to increase by 1.6 to 11.5 mmoles/day in 5 of the 6 patients studied. 24,25-DHCC increased intestinal absorption of calcium equally well in anephric patients, suggesting that conversion of 24,25-DHCC to 1,24,25-trihydroxycholecalciferol by the kidney cannot be the sole mechanism by which 24,25-DHCC expresses biological activity, even though in vitamin D deficient rats nephrectomy does abolish the ability of large doses of 24,25-DHCC to increase calcium absorption. It is concluded that 24,25-DHCC may be a calcium-regulating hormone in man. In view of the effects demonstrated here and its relatively high concentration in plasma and slow turnover rate, 24,25-DHCC has the properties that might be ideal for a long-acting stimulator of bone mineralisation. Further work is needed to explain why 24,25-DHCC has effects in man which are not readily seen in other species.
D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002116:Calcitonin; D002118:Calcium