Influence of vitamin D3 states, phenobarbital, and diphenylhydantoin treatment on the plasma 25-hydroxyvitamin D3 concentrations in the rat

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Abstract
The plasma 25-hydroxyvitamin D3 (25(OH)D3) response to a single intraportal injection of 100 μg∙kg−1 of vitamin D3 (D3) was determined before as well as 24 and 48 h after D3 administration in male Sprague-Dawley rats following a 3-week treatment with phenobarbital (PB), diphenylhydantoin (DPH), or the combination of the two drugs during normal vitamin D status (D+) or vitamin D deficiency (D−). Before D3 injection, plasma 25(OH)D3 concentrations were not statistically affected by the anticonvulsant (ACV) drug treatment in the D+ group and were at undetectable levels in the D− group. Twenty-four hours after D3, mean plasma 25(OH)D3 concentrations in the D− rats varied between 24.4 and 76.7 ng∙mL−1 while, in the D+ animals, the mean concentrats varied between 28.3 and 50.1 ng∙mL−1. The factorial analysis of variance revealed a significant effect of the drug treatment on plasma 25(OH)D3, concentrations in all groups (p < 0.005), a nonsignificant effect of the deficiency but a statistically significant positive interaction between PB and the D− state (p < 0.001). In the subsequent 24 h, 25(OH)D3 concentrations did not change significantly in both D− and D+ controls; in ACV drug treated animals, the plasma 25(OH)D3 concentrations dropped in D− animals only, revealing a statistically significant effect of the deficiency on plasma 25(OH)D3 (p < 0.001). These observations suggest that (1) during constant intake of D3, plasma 25(OH)D3 concentrations are not affected by ACV drug treatment; (2) 24 h after an acute D3 load, the plasma 25(OH)D3 concentrations attained are (a) independent of D3 nutritional status, (b) stimulated by ACV drug treatment both in the D+ and D− states, and (c) potentiated by PB treatment during D deficiency; (3) 48 h after D3 administration, ACV drug treatment contributes, in the D− state, to accelerate the plasma 25(OH)D3 disappearance; and (4) the effects of PB on plasma 25(OH)D3 concentrations are more pronounced than those of DPH and not potentiated by the combined drug treatment.

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