Effect of butalbital and phenobarbital pretreatment on antipyrine clearance in the rat.

The disposition kinetics of antipyrine after a single i.v. dose (75 mg/kg) of [14C]antipyrine were examined in control rats and in rats pretreated with butalbital and phenobarbital. Blood antipyrine data indicated that daily administration of phenobarbital (50 mg/kg) for 14 days resulted in significantly more rapid elimination of antipyrine than that observed after equal doses of butalbital, which was in turn significantly faster than the control values. Results of additional antipyrine tests after phenobarbital pretreatment for 2 and 5 days showed considerable enzyme induction after only 2 days of exposure to phenobarbital; the mean antipyrine clearance after the 2-day pretreatment was not significantly different from those after the 5- and 14-day pretreatments. The data suggested that the maximum increase in antipyrine clearance, ca. 190% of the control value, was achieved after approximately 5 daily doses of phenobarbital and maintained until the end of the 14-day pretreatment period. The subsequent decline in the induced enzyme activity, assessed by the antipyrine clearance values on days 1, 3, 6, and 9 post-phenobarbital treatment, appeared to be mono-exponential with a half-time of 3.8 days. Thus, the enzyme activity would return to baseline at ca. 15 days after the last dose of phenobarbital. In these studies, consistent increases in liver weight with increasing antipyrine clearance were observed, while no apparent relationship between antipyrine distribution volume and barbiturate pretreatment was found.