Biomedical Effects of 1A,25-dihydroxycholecalciferol

1,25-dihydroxycholecalciferol, also called Calcitriol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups which was identified

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Many 1A,25-dihydroxycholecalciferol analogs are readily absorbed from the GI tract following oral administration if fat absorption is normal. The presence of bile is required for absorption of ergocalciferol and the extent of GI absorption may be decreased in patients with hepatic, biliary, or GI disease (e.g., Crohn's disease, Whipple's disease, sprue). Because vitamin D is fat soluble, it is incorporated into chylomicrons and absorbed via the lymphatic system; approximately 80% of ingested 1A,25-dihydroxycholecalciferol appears to be absorbed systemically through this mechanism, principally in the small intestine. Although some evidence suggested that intestinal absorption of vitamin D may be decreased in geriatric adults, other evidence did not show clinically important age-related alterations in GI absorption of the vitamin in therapeutic doses. It currently is not known whether aging alters the GI absorption of physiologic amounts of 1A,25-dihydroxycholecalciferol.

After oral administration of calcitriol, there is about a 2-hour lag-time before calcium absorption in the GI tract increases. Maximal hypercalcemic effect occurs in about 10 hours, and the duration of action of calcitriol is 3-5 days.

Time to peak serum concentration: Oral: Approximately 3 to 6 hours.

The primary route of excretion of 1A,25-dihydroxycholecalciferol is the bile; only a small percentage of an administered dose is found in urine.

1A,25-dihydroxycholecalciferol and its metabolites undergo extensive enterohepatic recirculation, and patients who have undergone intestinal bypass surgery or who otherwise have severe shortening or inflammation of the small intestine fail to reabsorb vitamin D sufficiently to maintain normal 1A,25-dihydroxycholecalciferol nutriture.

Stored mainly in liver and other fat depots.

The metabolites of vitamin D analogs are excreted principally in bile and feces. Although some vitamin D that is excreted in bile is reabsorbed in the small intestine, enterohepatic circulation does not appear to be an important mechanism for conservation of the vitamin. Following oral or IV administration of a single dose of radiolabeled calcitriol, 19-41% of radioactivity is recovered in urine within 6-10 days.
It is not known whether this drug is excreted in human milk.

A specific 1,25-dihydroxycholecalciferol-binding protein was detected in high-salt cytosols prepared from human medullary thyroid carcinomas. The binding protein had the same equilibrium dissociation constant and sedimentation coefficient on sucrose gradients as that seen in established 1A,25-dihydroxycholecalciferol target tissues. This protein was not detected in normal thyroid cytosols, which may reflect the low proprotion of C-cells within the gland.

The serum concentrations of total calcium and 1,25-dihydroxyvitamin D3 (I) were measured in women during a menstrual cycle. A rise in the serum I level was observed on day 15 of the cycle without a detectable change in the serum calcium level. The I level on day 15 was double the values observed at days 1 and 8 of the cycle. The peak of I on day 15 was not observed in women ingesting oral contraceptives, suggesting that ovulation or its hormonal control was involved in the peak on day 15. A small but significant fall in the serum calcium concentration occured in the women ingesting oral contraceptives. In view of these findings the serum concentrations of I in women with functioning ovaries must be interpreted in the context of the stage of the menstrual cycle when the blood sample was obtained.