AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 5 627-G635, Copyright © 1986 by American Physiological Society
Influence of phenobarbital on the hepatic handling of [3H]vitamin D3 in the dog
M. Gascon-Barre, S. Vallieres and P. M. Huet
The effect of phenobarbital (PB) on the hepatic handling of vitamin D3 (D3)
and its metabolism to 25-hydroxyvitamin D3 [25(OH)D3] was studied in eight
mongrel dogs. The hepatic uptake and clearance of [3H]D3 were evaluated by
the multiple indicator-dilution curve technique, and the formation of
[3H]25(OH)D3 was evaluated by sampling the hepatic effluent. The hepatic
enzyme induction was assessed in six dogs by the 14CO2 breath excretion
test. The results show that the hepatic uptake of [3H]D3 was not
significantly affected but that its hepatic clearance was significantly
increased during PB treatment. The [3H]25(OH)D3 production was increased
during PB administration by a factor of 3-5 times over the pre- or post-PB
period. Evaluation of the enzyme induction produced by PB revealed that two
of the dogs studied had a blunted response to PB; furthermore, these dogs
were the only animals that showed no increase in [3H]25(OH)D3 production
during PB treatment and that in the presence of similar serum PB,
endogenous 25(OH)D3 and 1,25-dihydroxyvitamin D3 pools, and hepatic uptake
and clearance of [3H]D3. Strong positive correlation coefficients were
observed between the breath excretion of 14CO2 and the [3H]25(OH)D3
production during PB treatment, whereas no correlation was present in the
absence of PB. These observations show that, in most animals, PB is
accompanied by an increased hepatic clearance of [3H]D3 and by an increased
production of [3H]25(OH)D3. The data obtained during the present study also
show that the response to PB is heterogeneous and that some animals escaped
PB-mediated enzyme induction.(ABSTRACT TRUNCATED AT 250 WORDS)
