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Serum Dihydrotachysterol Levels and Biological Action in Normal Man^*

Metabolic Bone Disease Laboratory, Alfred I. duPont Institute, (A.T., M.E.N.) Wilmington, Delaware 19899
The Department of Pediatrics, Jefferson Medical College (M.E.N.) Philadelphia, Pennsylvania 19107
University of California and Veterans Administration Medical Center San Francisco, California 94121 (D.D.B.)

Address all correspondence and requests for reprints to: Arlene Taylor, Research Department, Alfred I. duPont Institute, P.O. Box 269, Wilmington, Delaware 19899.

Dihydrotachysterol (DHT₂) has been a safe and effective treatment for hypocalcemic disorders for many years, but few assays for quantitation of DHT₂ have been developed. Thus little is known about its pharmacokinetics. The 2-fold purpose of this study was 1) to develop a practical method for quantitating DHT₂ after oral dosing in normal subjects, and 2) to assess changes in serum DHT₂ levels and calcium and phosphorus metabolism after DHT₂ administration for 8 days. Peak serum DHT₂ levels in six normal subjects, assayed by high performance liquid chromatography were achieved 4 h after administration of 0.4–0.8 mg DHT₂; at 24 h, levels had declined by 70% whether DHT₂ had been given for 1 or 8 days. These data indicate that a standard approach is needed to interpret the results of serum DHT₂ measurements in treated patients. Interfering substances were detected in lipemic serum. The major biological effects of DHT₂ administration were hypercalciuria in two subjects and a fall in serum 1,25-dihydroxyvitamin D[1,25-(OH)₂D] levels, including free levels when measured, in all subjects. Possible explanations for this fall in serum 1,25- (OH)₂D levels include decreased 1,25-(OH)₂D production because of competition for the 1-hydroxylase enzyme by a metabolite(s) of DHT or increased metabolic clearance of 1,25-(OH)₂D.

^* This work was supported in part by a grant from Roxane Laboratories (Columbus, OH) and a grant from the NIH (AR-38955).

Received January 20, 1987.