In vivo metabolism of 24 R,25-dihydroxyvitamin D3: structure of its major bile metabolite

摘要: In vivo metabolism of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) in female dogs has been studied thoroughly, and its major bile metabolite identified. After single oral administration 24,25-(OH)2 [6,19,19-3H]D3 the plasma concentrations radioactive metabolites were monitored for 504 h, collected analyzed. The concentration 24,25-(OH)2D3 reached a maximum after 6 h decayed two distinct phases; fast-phase with half-life 17 followed by slow-phase 17-day half-life. area under concentration/time curve (AUC) was 78-84% (0-504 h). only detectable 25-hydroxy-24-oxovitamin whose AUC less than 5%. At about 50% administered radioactivity excreted, which 90% found feces, indicating most to be excreted bile. A metabolite, constituted 23% total at This efficiently deconjugated beta-glucuronidase afford an aglycone identified as 23S,25-dihydroxy-24-oxovitamin (23S,25-(OH)2-24-oxo-D3), co-chromatography on HPLC synthetic standards. glucuronide isolated from given large doses 24,25-(OH)2D3, structure determined being 23-(beta-glucuronide) 23S,25-(OH)2-24-oxo-D3, analyzing negative ion mass spectrum positive derivatives. Thus it concluded that, dogs, is long lasting vitamin D mainly when metabolized 23S,25-(OH)2-24-oxo-D3 conjugated 23-OH glucuronide.