Development and regression of the hepatic microsomal enzyme induction and stimulation of biliary excretion produced by phenobarbital in rats.
The time-course effect of a single dose (75 mg/kg i.p.) of phenobarbital (PB) and that of prolonged PB treatment (75 mg/kg daily i.p., for 1 to 5 days) on the hepatic excretory and microsomal enzyme functions have been studied in rats. PB given in a single dose resulted in hypercholeresis 6 hr, an increase in the biliary excretion rate of bromcresol green and in hepatic cytochrome P-45 concentration 12 hr, and shortening of hexobarbital sleeping time 24 hr after the administration. All these changes, except the hypercholeresis, became gradually more apparent following the repeated daily administration of PB. Regression of the changes was faster in biliary excretory function than in microsomal function. Biliary flow and biliary output of bromcresol green returned to the control level at 72 hr after a single dose of PB or at 5 days after the cessation of a 5-day PB treatment, whereas enzyme induction was still apparent at those times. These results indicate that no close correlation in time exists between PB produced hepatic microsomal enzyme induction and the stimulatory effect of PB on biliary excretion.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects*; D006591:Hexobarbital / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors
D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D010634:Phenobarbital