The time course of inductions of N-demethylation and pentobarbital hydroxylation of hepatic drug metabolizing system in continuous pentobarbital administration by pentobarbital pellet implantation in the mouse is presented. The results also demonstrate that hepatic microsomal drug-metabolizing enzymes in the mouse could be induced much faster by a single pentobarbital pellet implantation than by the ordinary parenteral administration technique. The reduction of pentobarbital half-life (T 1 2) in plasma, brain and liver of the animals which had been implanted with a pentobarbital pellet also substantiates the acceleration of pentobarbital metabolism in the mouse by the pellet implantation method. The results show that the T 1 2 of pentobarbital in plasma, brain and liver of pentobarbital pellet implanted groups is only 1 2, 1 6 and 1 9 of that of the placebo control group, respectively. The studies on urinary excretion of pentobarbital and its metabolites also reveals that pentobarbital pellet implantation induced much faster rate of metabolism of pentobarbital in the mouse.
Bibliographical noteFunding Information:
These studies were supported by NIDA grant DA-01403 . H . H . Loh is a recipient of a NIMH Research Scientist Development Award, K2-DA-70554 . The authors wish to thank Mrs . Susan Culbertson for assistance in preparation of the manuscript .