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Decreased Liver and Lung Drug-metabolizing Activity in Mice Treated with Corynebacterium parvum¹

Departments of Pharmacology [L. F. S., W. G. H., S. E. K.] and Surgery [R. S. F.], College of Medicine, University of Vermont, Burlington, Vermont 05401

Injections of killed suspensions of Corynebacterium parvum (i.p.) in young male mice were followed by time- and dose-dependent decreases in the drug-metabolizing activity of liver microsomes and lung homogenates. In vitro assays with model substrates [aminopyrine, aniline, p-nitroanisole, and benzo(a)pyrene] were used to quantitate drug-metabolizing activity. It is likely that such decreases in mixed-function oxidase activity will act to significantly alter the pharmacokinetics of concurrently or subsequently administered drugs. The results provide a possible mechanism to explain several previously reported immunochemotherapeutic interactions.

¹ This work was supported in part by Grant HD-08708 from the National Institute of Child Health and Human Development.

Received 6/22/76. Accepted 8/24/76.