Abstract
The O-demethylation of 14C-griseofulvin by liver microsomes has been studied in rats and mice treated with phenobarbital, 3-methylcholanthrene, and griseofulvin. Phenobarbital treatment increased 4-and 6-demethylation of 14C-griseofulvin in rats and mice. Treatment with 3-methylcholanthrene increased both 4- and 6-demethylation in mice but only 6-demethylation in rats. Prolonged intake of griseofulvin increased 6-demethylation but not 4-demethylation in rats and mice. Based on this differential stimulation of 4- and 6-demethylation by phenobarbital. 3-methylcholanthrene, and griseofulvin in rats and mice, it is suggested that 4-demethylation and 6-demethylation of griseofulvin in liver microsomes of rats and mice are probably catalyzed by two different enzymes. In mice. griseofulvin treatment has been shown to stimulate benzpyrene hydroxylation and benzphetamine demethylation. It also caused a marked increase in smooth endoplasmic reticulum and liver weight, but not in concentrations of cytochrome P-450 and microsomal protein.
Footnotes
- Received July 7, 1972.
- Accepted March 2, 1973.
- Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics
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