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Serum dihydrotachysterol levels and biological action in normal man.

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 alpha-hydroxylase enzyme by a metabolite(s) of DHT or increased metabolic clearance of 1,25-(OH)2D.