The half-lives described thus far probably relate to plasma and extravascular fluid and tissues of the shared compartment. Differences in DBP binding affinity also exist for 25(OH)D 2 and 25(OH)D 3, and it was recently shown directly that 25(OH)D 2 half-life is shorter than 25(OH)D 3 half-life and that half-life is influenced by DBP concentration and genotype (see Influence of DBP Genotype and Concentration on Vitamin D Metabolism and 25(OH)D Half-Life section). The importance of DBP binding in vitamin D metabolism was demonstrated in DBP-null mice in which 25(OH)D and vitamin D half-lives were dramatically reduced, and hepatic uptake, metabolism, and excretion of vitamin D were increased. Greater binding affinity effectively protects the molecule from hydroxylation, allowing a longer half-life. Vitamin D metabolites differ in their affinity for DBP (25(OH)D ≈ 24,25(OH) 2D > 1,25(OH) 2D > vitamin D), and this may provide some explanation for the differences in half-lives. The 1,25(OH) 2D production rate was estimated to be between 0.35 and 8.1 nmol/day using a compartmental modeling approach. For 1,25(OH) 2D 3, although values up to 80 h have been reported, most other studies have reported shorter half-lives between 5 and 28 h after intravenous and oral administration of labeled and unlabeled doses. For vitamin D 3 plasma half-lives of 0.5–5 days are reported, 10–40 days for 25(OH)D 3, slightly shorter values for 25(OH)D 2 and 6–34 d (means of 7 and 16 days) for 24,25(OH) 2D 3. Reported values for plasma half-lives for each metabolite may differ dependent on methodology but are within a reasonably consistent range. Plasma half-lives for each of the vitamin D metabolites are very different ( Table 37.1). Jones, in Vitamin D (Fourth Edition), 2018 Plasma Half-Lives of Vitamin D Metabolites
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