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 less than 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 less than 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]-25-(OH)2D. Age- and weight-matched rats treated for five days with DPH (75 mg/kg/day), however, had significantly (P less than 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 less than 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.
D015652:25-Hydroxyvitamin D 2; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004872:Ergocalciferols / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010634:Phenobarbital / Q000633:toxicity*; D010672:Phenytoin / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000378:metabolism*
D004872:Ergocalciferols; D010281:Parathyroid Hormone; D014807:Vitamin D; D015652:25-Hydroxyvitamin D 2; C003564:1,25-dihydroxyergocalciferol; D010672:Phenytoin; D010634:Phenobarbital