Renal cortical accumulation of phenobarbital in rats and rabbits: lack of correlation with induction of renal microsomal monooxygenases.
Subchronic treatment with phenobarbital induces renal cortical microsomal monooxygenase activities (e.g., ethoxycoumarin O-deethylase, benzphetamine N-demethylase and arylhydrocarbon hydroxylase) and cytochrome P-450 content in rabbits but not in rats. The mechanism responsible for this species-specific difference in renal cortical enzyme induction remains unknown, but may be the result of differences in the renal cortical accumulation of phenobarbital by these two species. Rabbit kidneys may be capable of accumulating more phenobarbital than rat kidneys. In the present study, accumulation of phenobarbital by renal cortical slices and the disposition of phenobarbital in vivo were determined. Both rat and rabbit renal cortical accumulation of phenobarbital was partially energy-dependent and inhibited by SKF-525A. Renal cortical accumulation of phenobarbital in rats was also inhibited by piperonyl butoxide. Accumulation of phenobarbital in rabbit renal cortical slices was not greater than that in rat renal cortical slices. Furthermore, rabbit renal cortex did not accumulate more phenobarbital in vivo than rat renal cortex. These results suggest that the different enzyme inducing effects of phenobarbital in rat and rabbit kidneys is not due to quantitative differences in accumulation of phenobarbital in renal cortex.
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors
D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D010634:Phenobarbital