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Comparison of effects of 1 alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man.
J Clin Invest. 1976 Jun; 57(6):1540-7.JCI

Abstract

The effects of short-term treatment with 1,25-dihydroxy-vitamin D3 [1,25(0H)2D3] or 1 alpha-hydroxy-vitamin D3 [1 alpha(OH)D3] on intestinal absorption of 47Ca were compared in 41 experiments in normals and 72 experiments in patients with chronic renal failure. 11 patients were studied a second time after treatment for 2-5 mo. Doses varied from 0.14 to 5.4 mug/day to establish dose-response relationships. Urinary calcium was monitored in normal subjects, nine of whom received a constant calcium intake on a metabolic unit. There was an increase in intestinal absorption of 47Ca and urinary calcium in normals receiving 1,25 (OH)2D3, 0.14 mug/day or greater, and 0.28 mug/day or greater augmented intestinal absorption of 47Ca in chronic renal failure. In contrast, 2.6 mug/day of 1 alpha (OH) D3 was required to increase intestinal absorption of 47Ca in both groups. The increase in urinary calcium to maximal levels was delayed during treatment with 1 alpha (OH) D3, 5-10 days vs. 2-5 days with 1,25 (OH)2D3. Moreover, half times for urinary calcium to decrease to pretreatment levels after stopping treatment were greater after 1 alpha-(OH) D3 (1.5-2.7 days) than 1,25(OH)2D3 (1.1-2.0 days). With long-term administration there was a progressive increase in intestinal absorption of 47Ca in the patients receiving 1 alpha (OH)D3; this was not observed with 1,25(OH)2D3. The pharmacologic differences between 1 alpha(OH) D3 and 1,25(OH)2D3 may be explained by the requirement for 25-hydroxylation of 1alpha(OH) D3 before biologic effects occur; at low doses (less than 1 mug/day), 1 alpha(OH) D3 competes with vitamin D3 for 25-hydroxylation. With prolonged treatment or larger doses (greater than 2 mug/day),, 1alpha(OH) D3 could accumulate and then be hydroxylated resulting in production of higher levels of 1,25(OH)2D3.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

932193

Citation

Brickman, A S., et al. "Comparison of Effects of 1 Alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in Man." The Journal of Clinical Investigation, vol. 57, no. 6, 1976, pp. 1540-7.
Brickman AS, Coburn JW, Friedman GR, et al. Comparison of effects of 1 alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man. J Clin Invest. 1976;57(6):1540-7.
Brickman, A. S., Coburn, J. W., Friedman, G. R., Okamura, W. H., Massry, S. G., & Norman, A. W. (1976). Comparison of effects of 1 alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man. The Journal of Clinical Investigation, 57(6), 1540-7.
Brickman AS, et al. Comparison of Effects of 1 Alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in Man. J Clin Invest. 1976;57(6):1540-7. PubMed PMID: 932193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of effects of 1 alpha-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man. AU - Brickman,A S, AU - Coburn,J W, AU - Friedman,G R, AU - Okamura,W H, AU - Massry,S G, AU - Norman,A W, PY - 1976/6/1/pubmed PY - 1976/6/1/medline PY - 1976/6/1/entrez SP - 1540 EP - 7 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 57 IS - 6 N2 - The effects of short-term treatment with 1,25-dihydroxy-vitamin D3 [1,25(0H)2D3] or 1 alpha-hydroxy-vitamin D3 [1 alpha(OH)D3] on intestinal absorption of 47Ca were compared in 41 experiments in normals and 72 experiments in patients with chronic renal failure. 11 patients were studied a second time after treatment for 2-5 mo. Doses varied from 0.14 to 5.4 mug/day to establish dose-response relationships. Urinary calcium was monitored in normal subjects, nine of whom received a constant calcium intake on a metabolic unit. There was an increase in intestinal absorption of 47Ca and urinary calcium in normals receiving 1,25 (OH)2D3, 0.14 mug/day or greater, and 0.28 mug/day or greater augmented intestinal absorption of 47Ca in chronic renal failure. In contrast, 2.6 mug/day of 1 alpha (OH) D3 was required to increase intestinal absorption of 47Ca in both groups. The increase in urinary calcium to maximal levels was delayed during treatment with 1 alpha (OH) D3, 5-10 days vs. 2-5 days with 1,25 (OH)2D3. Moreover, half times for urinary calcium to decrease to pretreatment levels after stopping treatment were greater after 1 alpha-(OH) D3 (1.5-2.7 days) than 1,25(OH)2D3 (1.1-2.0 days). With long-term administration there was a progressive increase in intestinal absorption of 47Ca in the patients receiving 1 alpha (OH)D3; this was not observed with 1,25(OH)2D3. The pharmacologic differences between 1 alpha(OH) D3 and 1,25(OH)2D3 may be explained by the requirement for 25-hydroxylation of 1alpha(OH) D3 before biologic effects occur; at low doses (less than 1 mug/day), 1 alpha(OH) D3 competes with vitamin D3 for 25-hydroxylation. With prolonged treatment or larger doses (greater than 2 mug/day),, 1alpha(OH) D3 could accumulate and then be hydroxylated resulting in production of higher levels of 1,25(OH)2D3. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/932193/Comparison_of_effects_of_1_alpha_hydroxy_vitamin_D3_and_125_dihydroxy_vitamin_D3_in_man_ L2 - https://doi.org/10.1172/JCI108424 DB - PRIME DP - Unbound Medicine ER -