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Ketoconazole reduces elevated serum levels of 1,25-dihydroxy vitamin D in hypercalcemic sarcoidosis

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Abstract

The antifungal drug ketoconazole, a cytochrome P450 inhibitor, has been shown to inhibit renal 1,25-dihydroxyvitamin D production in vitro and to lower serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with primary hyperparathyroidism. To assess the usefulness of this drug in the hypercalcemia of sarcoidosis, a condition thought to result from over-production of 1,25-dihydroxyvitamin D by sarcoid-involved tissues, two men with sarcoidosis, hypercalcemia, and elevated serum levels of 1,25-dihydroxy-vitamin D were given ketoconazole, 600–800 mg per day, for four to six days. Serum 1,25-dihydroxyvitamin D levels were markedly reduced (by approximately 40%) in both patients during ketoconazole administration, but serum calcium was not affected. In both patients, renal function deteriorated during ketoconazole treatment. We conclude that ketoconazole administration can lower the elevated serum 1,25-dihydroxyvitamin D levels in sarcoidosis. However, deterioration of renal function during ketoconazole administration as well as failure of hypercalcemia to be affected during short-term ketoconazole treatment suggest that this drug might not be appropriate for acute treatment of hypercalcemic sarcoidosis.

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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

Fundmg was provided by the Department of Clinical Investigation, Walter Reed Army Medical Center and by USPHS grants RR-00058, DK-15089 and DK-22014.

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Glass, A.R., Cerletty, J.M., Elliott, W. et al. Ketoconazole reduces elevated serum levels of 1,25-dihydroxy vitamin D in hypercalcemic sarcoidosis. J Endocrinol Invest 13, 407–413 (1990). https://doi.org/10.1007/BF03350691

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