PHENOBARBITAL-INDUCED ALTERATIONS IN THE METABOLISM OF [VITAMIN-D3-H-3 BY THE PERFUSED RACHITIC RAT-LIVER INVITRO

Using an in vitro recycling hepatic perfusion system, 5 days of phenobarbital treatment increased hepatic production of [3H]25-hydroxyvitamin D3 (4.3 .+-. 0.3 vs. 3.3 .+-. 0.2%/h, P < 0.025) without affecting the biliary excretion of radioactivity. Rachitic livers perfused with blood obtained from animals treated with phenobarbital for 5 days also manifested an increase in [3H]25-hydroxyvitamin D3 production (4.6 .+-. 0.5 vs. 3.3 .+-. 0.2%/h, P < 0.02). Addition of phenobarbital or its major metabolite, p-hydroxyphenobarbital, directly to the perfusion apparatus had no effect on [3H]25-hydroxyvitamin D3 production. Phenobarbital treatment was also attended by a decrease in the intrahepatic content of [3H]vitamin D3 (11.7 .+-. 0.4 vs. 17.5 .+-. 0.7 dpm/mg liver protein, P < 0.001) without alterations in the content of [3H]25-hydroxyvitamin D3. The increased hepatic conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 attending phenobarbital treatment is evidently secondary to stimulation of the hepatic 25-hydroxylation system(s) by a metabolite of phenobarbital other than p-hydroxyphenobarbital and/or by metabolic alterations resulting from phenobarbital therapy.