Abstract
The action of cholecalciferol (vitamin D 3) (D 3) and two of its active metabolites, 25-hydroxy-cholecalciferol (25-OH-D 3) and 1,25-dihydroxycholecalciferol (1,25-(OH) 2-D 3), was studied in phenobar-bital-treated and untreated rachitic chicks by means of a bioassay for intestinal calcium absorption and bone resorption. Phenobarbital treatment (7 days) reduced the ability of single doses (0.65 to 3.5 nmoles) of D 3 and 25-OH-D 3 to stimulate intestinal calcium absorption and bone resorption. The impaired biological responses to these moderate doses of D 3 could be overcome by increasing the dose (32.5 nmoles). In contrast, administration of small doses of 1,25-(OH) 2-D 3 (0.26 nmole) stimulated both the intestinal calcium transport and bone resorption responses in phenobarbital-treated chicks. Moreover, phenobarbital treatment appeared to enhance the calcemie response of bone to 1,25-(OH) 2-D 3. The metabolism of radioactive D 3 was also studied in control rachitic chicks and rachitic chicks treated with phenobarbital for 7 days. Sephadex LH-20 column chromatography of lipid-soluble extracts of blood, intestinal mucosa and bone was carried out 24 hr after administration of a single dose of 4- 14C-vitamin D 3. The anticonvulsant treatment resulted in markedly lower quantities of 1,25-(OH) 2-D 3 in the bone, but with no major changes in the amount of this steroid present in the intestine. The drug treatment also resulted in increased amounts of D 3 and 25-OH-D 3 in the blood and intestinal mucosa. Seven-day anticonvulsant treatment of the rachitic chick clearly impairs the biological responses to D 3 and also alters its metabolism. It is possible that the reported high incidence of osteomalacia occurring in patients on long-term anticonvulsant therapy may possibly be caused by derangements in the conversion of D 3 to its biologically active metabolites and in their association with the target tissues. This may provide some explanation for the disruption of normal calcium metabolism which occurs after chronic administration of phenobarbital and other related drugs.
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