AJP - Endocrinology and Metabolism, Vol 245, Issue 1 55-E59, Copyright © 1983 by American Physiological Society
Effect of phenobarbital treatment on metabolism of vitamin D by rat liver
D. T. Baran
Phenobarbital has been postulated to impair hepatic conversion of vitamin D
to 25-hydroxyvitamin D [25(OH)D] either by accelerating the conversion of
vitamin D to biologically inactive products or by directly inhibiting
25(OH)D production. The effect of a dose of phenobarbital documented to
decrease circulating 25(OH)D levels on hepatic vitamin D metabolism has
been investigated in rachitic rats with a recycling in vitro hepatic
perfusion system. Phenobarbital (75 mg/kg/day) administered
intraperitoneally to D-replete rats increased circulating 25(OH)D blood
levels after 4 wk of therapy but was attended by decreased levels after 6
and 8 wk. Rachitic rats were then injected daily with phenobarbital for
either 4 or 8 wk and the livers removed and perfused at a rate of 15 ml/min
for 3 h. The concentrations of [3H]25(OH)D in the hepatic perfusate at 3 h
was decreased after both 4 and 8 wk of phenobarbital. Although total
[3H]-25(OH)D production (hepatic plus perfusate) was unaffected by
phenobarbital, the efficiency of hepatic production was decreased after 8
wk of treatment and the release of [3H]-25(OH)D from the liver into the
perfusate was inhibited after both 4 and 8 wk. The data indicate that
chronic phenobarbital therapy decreases both the release of [3H]25(OH)D
from the liver into the perfusate and the efficiency of hepatic
[3H]-25(OH)D production. Phenobarbital-induced inhibition of 25(OH)D
release from the liver may be another mechanism for the low 25(OH)D levels
noted in humans after long-term phenobarbital therapy.
