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Journal of Clinical Endocrinology & Metabolism Vol. 66, No. 5 934-938
doi:10.1210/jcem-66-5-934
Copyright © 1988 by the Endocrine Society.
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Ketoconazole-Induced Reduction in Serum 1,25-Dihydroxyvitamin D and Total Serum Calcium in Hypercalcemic Patients*

ALLAN R. GLASS and CHARLES EIL

Departments of Medicine and Clinical Investigation, Walter Reed Army Medical Center Washington, D.C. 20307
the Department of Medicine, Uniformed Services University of the Health Sciences Bethesda, Maryland 20814
the Department of Medicine, Brown University Providence, Rhode Island 02908

Address all correspondence and requests for reprints to: Allan R. Glass, M.D., Endocrinology Service, 7D, Walter Reed Army Medical Center, Washington, D.C. 20307-5001.

Administration of the antifungal drug ketoconazole reduces serum 1,25-dihydroxyvitamin D (1,25-D) levels in normal subjects. To determine whether a similar effect occurs in hypercalcemic patients, ketoconazole (200 mg every 8 h for 7 days) was given to nine patients with confirmed primary hyperparathyroidism, three patients with probable primary hyperparathyroidism who were awaiting surgery, and three patients with mild hypercalcemia of uncertain etiology who were being followed. Ketoconazole administration led to a significant reduction in mean serum 1,25-D levels in the hypercalcemic patients [basal, 64 ± 7 (±SEM) pg/mL (154 ± 17 pmol/L) vs. 36 ± 5 pg/mL (86 ± 12 pmol/L) after ketoconazole; P < 0.001]. Serum total calcium fell slightly but significantly [basal, 11.05 ± 0.17 mg/dL (2.76 ± 0.04 mmol/L) vs. 10.77 ± 0.16 (2.69 ± 0.04 mmol/L) after ketoconazole; P < 0.02], but the falls in total serum calcium and serum 1,25-D after ketoconazole treatment were not correlated with one another. Ketoconazole administration did not alter serum ionized calcium, 25-hydroxyvitamin D, phosphate, alkaline phosphatase, or PTH concentrations or urinary cAMP excretion. The responses to ketoconazole were similar in all three patient subgroups. We conclude that short term administration of ketoconazole to hypercalcemic patients causes a substantial fall in serum 1,25-D and a small fall in total serum calcium. These effects render ketoconazole a potentially useful agent for investigation of the importance of 1,25-D in patients with hypercalcemic disorders and for their treatment

* 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. This work was supported by the Department of Clinical Investigation, Walter Reed Army Medical Center.

Received October 5, 1987.




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Copyright © 1988 by The Endocrine Society