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Science 23 June 1972:
Vol. 176. no. 4041, pp. 1341 - 1343
DOI: 10.1126/science.176.4041.1341
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Articles

Destruction of Cytochrome P450 by Secobarbital and Other Barbiturates Containing Allyl Groups

W. Levin 1, E. Sernatinger 1, M. Jacobson 1, and R. Kuntzman 1

1 Department of Biochemistry and Drug Metabolism, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110

Administration of certain commonly used barbiturates containing allyl groups, such as secobarbital, allobarbital, or aprobarbital to rats treated chronically with a microsomal enzyme inducer causes a rapid destruction of the liver microsomal hemoprotein that serves as the terminal oxidase for drug metabolism. In contrast, barbiturates without an allyl group do not have this effect. The decrease in this hemoprotein, cytochrome P450, by the barbiturates containing an allyl group could also be demonstrated in an in vitro liver microsomal system requiring reduced nicotinamide adenine dinucleotide phosphate. These results suggest that the barbiturates containing an allyl group are converted to a metabolite that leads to the destruction of cytochrome P450.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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