The distribution of (5E)-(10S)-10, 19-dihydroercalciol and its metabolites in serum of rats

Abstract

The distribution of radioactivity in serum of male rats (275 g) after oral administration of tritium labelled (5E)-(10S)-10, 19-dihydroercalciol (dihydrotachysterol 2) has been studied as a function of time and dose level. Nine distinct radioactive substances, chromatographing in the range between calciol and calcitriol, could be demonstrated. No attempt was made to establish chemical structures. After a single dose of 1.84 nmol, (5E)-(10S)-10, 19-dihydroercalciol is very rapidly metabolized to more polar forms. The time course of appearance, ranging between 30 min and 1 day after administration, and the polarity of these substances indicated that they might be formed in sequence. The highest serum concentrations of the major substances occurred between 2 h and 10 h after administration, but compared with the dosage they were very low. In response to daily administration the concentrations of the major substances achieved steady-state levels within 1–4 days. The metabolism of (5E)-(10S)-10, 19-dihydroercalciol was apparently not affected by its nutritional status at the dose level studied. After single administration of progressively increasing doses, ranging from 1.84 nmol to 1.84μmol, the relative increments of the concentrations of the major substances rose in proportion to the relative increases of the dosage. The mechanisms responsible for the appearance of these substances in serum were found to be closely related. At dose levels up to 18.4 nmol feedback control was apparently absent.