Effect of liver microsome enzyme-inducing drugs on blood serum pentobarbital clearance and sleep time in sheep and rabbits.

Sheep were administered phenobarbital, diphenylhydantoin, chlorcyclizine, or phenylbutazone over 27 days. Rabbits were administered phenobarbital, diphenylhydantoin, or chlorcyclizine for 15 days. After the last treatment, pentobarbital was administered intravenously, and measurements were made of sleep time and blood serum pentobarbital concentrations over a 2-hour period. Treatment of ewes with phenobarbital or phenylbutazone increased the rate of pentobarbital clearance from the circulation and shortened sleep time; treatment with diphenylhydantoin or chlorcyclizine decreased the rates of pentobarbital clearance from blood and increased sleep time. Treatment of rabbits with phenobarbital or diphenylhydantoin accelerated pentobarbital clearance from blood and shortened sleep time; chlorcyclizine had no effect on blood pentobarbital concentrations or sleep time. The results suggest that accelerated or delayed clearance of pentobarbital from the circulation was largely responsible for shortened or prolonged sleep times. Other factors may have been involved to some extent in determining sleep time, because ewes with shortened sleep time tended to awake with lower circulating concentrations of pentobarbital than did control ewes, and those with prolonged sleep time tended to awake with higher pentobarbital values.