Serum dihydroxyvitamin d metabolite concentrations in patients on chronic anticonvulsant drug therapy: Response to pharmacologic doses of vitamin D 2

Abstract

We examined the effects of chronic anticonvulsant drug administration on the serum concentrations of dihydroxy-vitamin D metabolites and the response of these metabolite levels to short-term treatment with pharmacologic doses of vitamin D 2. Twelve patients maintained on chronic combined diphenylhydantoin and phenobarbital therapy were studied before and after the administration of vitamin D 2, 75,000 units/week for 6 weeks. Prior to vitamin D 2 administration, the patient group demonstrated decreased serum calcium ( P < 0.01) and increased serum iPTH ( P < 0.02) concentrations relative to 18 matched controls. Serum 250HD and 24,25(OH) 2D concentrations in the patient group were reduced by 38% and 75% ( P < 0.001), while serum 1,25(OH) 2D concentration was increased by 27% ( P < 0.05) relative to control values. After vitamin D administration serum calcium and iPTH concentrations in the patient group were restored to values that were not significantly different from control levels. Serum 250HD and 24,25(OH) 2D concentrations were increased by 4.6-and 6.3-fold, respectively, to supranormal levels. Serum 1,25(OH) 2D concentration exhibited an unexpected further 30% increase over pretreatment values, resulting in a return of the serum 1,25(OH) 2D/24,25(OH) 2D concentration ratio to a normal value. These data indicate that in patients treated chronically with anticonvulsant drugs, serum 250HD concentration responds appropriately to vitamin D2 administration, but regulation of renal dihydroxy metabolite formation may be altered.