Most vitamin D is excreted in the bile; less than 5% is excreted as water-soluble metabolites in urine. Some 2% to 3% of the vitamin D in bile is cholecalciferol, calcidiol, and calcitriol, but most is a variety of polar metabolites and their glucuronide conjugates. In most tissues, the major pathway for inactivation of calcitriol is by way of 24-hydroxylation to calcitetrol, then onward oxidation byway of the 24-oxo-derivative, 23-hydroxylation, and oxidation to calcitroic acid (see Figure 3.3). In addition, a variety of hydroxylated and other polar metabolites have been identified in bile, and many of these onward oxidation products also undergo glucuronide conjugation in the liver (Reddy and Tserng, 1989).
Compounds that induce cytochrome P450-dependent hydroxylases, such as barbiturates and the anticonvulsants primidone and diphenylhydantoin, cause increased output of vitamin D metabolites in the bile, and increase the rate of inactivation of calcidiol by liver microsomes. As a result of this, long-term use of these anticonvulsants may be associated with the development of osteomalacia, although barbiturates also cause some induction of calciferol 25-hydroxylase, thus increasing the hydroxylation of calciferol to calcidiol.
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