Anticonvulsant therapy and vitamin D metabolism: Evidence for different mechanisms for phenytoin and phenobarbital

Combined therapy of epileptic children with phenobarbital (PB) and phenytoin (DPH) significantly decreased serum 25-hydroxyvitamin D (25-OH-D) levels, whereas PB alone significantly increased serum 25-OH-D levels after one to two months of therapy [Sumi et al., 1978]. Studies were conducted in rats to test the hypothesis suggested by the human studies that DPH and PB had different effects on Vitamin D metabolism. Male Wistar rats treated for five days with PB (75 mg/kg/day) had significantly (P<0.05) decreased 1,25-dihydroxyvitamin D (1,25-(OH)₂D) levels (7.1 ± 1.6 ng/dl, mean ±SD) compared to controls (12.0 ± 4.0 ng/dl), and significantly (P<0.005) increased conversion of [³H]-vitamin D into [³H]-25-OH-D and [³H]-24,25-(OH)₂D, but no increased conversion into [³H]-1, 25-(OH)₂D. Age- and weight-matched rats treated for five days with DPH (75 mg/kg/day), however, had significantly (P<0.03) decreased 25-OH-D levels (41.9±5.7 ng/ml) compared to controls (52.4±4.4 ng/ml), and significantly (P<0.01) increased conversion into [³H]-1,25-(OH)₂D. These results are consistent with clinical data, which suggest that different alterations in vitamin D metabolism occur after short-term DPH versus PB therapy.