Acceleration of pentobarbital metabolism in tolerant mice induced by pentobarbital pellet implantation |
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Authors: | I Yamamoto IK Ho HH Loh |
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Institution: | 1. Department of Hygienic Chemistry Daiichi college of Pharmaceutical Sciences 93 Tamagawa, Fukuoka, Japan;2. Department of Pharmacology and Toxicology University of Mississippi Medical Center Jackson, Mississippi 39216, USA;3. Department of Pharmacology University of California, San Francisco San Francisco, California 94143, USA |
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Abstract: | 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 () 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 of pentobarbital in plasma, brain and liver of pentobarbital pellet implanted groups is only 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. |
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