Calcified Tissue International

, Volume 35, Issue 1, pp 376–382 | Cite as

Sequential changes in mineral metabolism and serum vitamin D metabolite concentrations produced by phenobarbital administration in the rat

  • Theodore J. Hahn
  • Linda R. Halstead
Laboratory Investigations


We examined the effect of daily phenobarbital administration on serum vitamin D metabolite levels and indices of vitamin D biologic activity in 7-week-old male rats maintained on parenteral vitamin D supplementation (125 ng/day). Treatment with phenobarbital (75 mg/kg/day) produced a biphasic response in parameters of vitamin D biologic effect, including serum calcium concentration, serum inorganic phosphate concentration, and intestinal45Ca calcium absorption. An initial increase in these values, maximal after 3–5 days of treatment, was followed by a subsequent decline to subnormal levels by day 21. A parallel biphasic pattern was observed for serum 25-hydroxyvitamin D (25OHD) concentration. Serum 25OHD reached a peak increase of 87% above control levels (P<0.01), observed after 5 days of treatment, and subsequently declined to 62% of control animal values (P<0.01) by 21 days. Serum 24,25(OH)2D concentration followed a similar course and exhibited a strong positive correlation with serum 25OHD concentrations (r=0.74,P<0.01). In contrast, serum 1,25(OH)2D concentration was not significantly different from control values after 5 days but was increased 80% over control values (P<0.05) by day 21. Serum vitamin D concentration declined progressively in treated animals, falling to 50% of control levels (P<0.05) by day 5 and to 27% of control levels (P<0.001) by day 21. At the point of maximal increase in serum 25OHD concentration, hepatic microsomal vitamin D3-25-hydroxylase activity was not increased in the treated animals whereas hepatic mitochondrial vitamin D3-25-hydroxylase activity was increased by 2.4-fold. Increased hepatic mitochondrial vitamin D3-25-hydroxylase activity persisted through 21 days of phenobarbital treatment. It is concluded that phenobarbital administration in the rat produces an initial increase in vitamin D biologic effect which correlates temporally with increased circulating levels of 25OHD, the latter possibly resulting from increased hepatic mitochondrial vitamin D-25-hydroxylase activity. A subsequent decline in serum 250HD concentration may be the result of decreased availability of vitamin D as substrate. This sequence of alterations in vitamin D metabolism bears potentially important implications for the timing of prophylactic vitamin D supplementation in patients treated with anticonvulsant drugs.

Key words

25-hydroxyvitamin D Phenobarbital Vitamin D biologic activity Drug-induced bone mineral disorders 


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Copyright information

© Springer-Verlag New York Inc. 1983

Authors and Affiliations

  • Theodore J. Hahn
    • 1
  • Linda R. Halstead
    • 1
  1. 1.Division of Bone and Mineral Metabolism, Department of MedicineWashington University School of Medicine, The Jewish Hospital of St. LouisSt. LouisUSA

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