Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by BERNSTEIN, J. R.
Right arrow Articles by FRANKLIN, R. B.
Right arrow Search for Related Content
PubMed
Right arrow Articles by BERNSTEIN, J. R.
Right arrow Articles by FRANKLIN, R. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1986 Oxford University Press

research-article

The Induction Profile of Three Orally Active Imidazopyridine-Containing Cardiotonic Agents in Rat Hepatic Microsomes

JOHN R. BERNSTEIN and RONALD B. FRANKLIN1

Department of Drug Disposition, Lilly Research Laboratories Eli Lilly Company, Lilly Corporate Center Indianapolis, Indiana 46285

The Induction Profile of Three Orally Active Imidazopyridine-Containing Cardiotonic Agents in Rat Hepatic Microsomes. BERNSTEIN, J. R, AND FRANKLIN, R. B., (1986). Fundam Appl. Toxicol. 7, 26-32. The induction of hepatic cytochrome P-450-linked monooxygenases has been studied after the twice daily, oral administration of two imidazo[4,5-c]pyridine-containing compounds and one imidazo[4,5-6]pyridine-containing drug. The compounds were administered by the oral route, at different doses, for 6 days after which time hepatic microsomes were prepared. In vitro biochemical assays revealed that all three compounds increased the O-deethylation of 7-ethoxyresorufin in a dose-dependent manner while not significantly affecting either the 0-de- alkylation of 7-ethoxycoumarin or the levels of NADPH-cytochrome c reductase. Ethylmorphine- N-demethylation was decreased after dosing with the imidazo[4,5-b]pyridine-containing drug. Levels of cytochrome(s) P-450 and liver-to-body weight ratios were not significantly altered. The imidazo[4,5-c]pyndine-containing compound was more potent in terms of the induction of 7-ethoxyresorufin than either of the imidazo[4,5-c]pyridine-containing compounds but was approximately fourfold less active in this regard than 3-methylcholanthrene. No induction of cy- tochrome-.P-450-linked monooxygenase activities was evident at a twice daily dose of 5 mg/kg for 6 days for all three compounds tested, constituting a no-effect level. The imidazo[4.5-c]pyridine-1 containing compounds exhibited modified Type II difference spectra when added to a suspension of rat hepatic microsomes. The imidazo[4,5-6]pyridine-containing compound has previously been reported to be (i) a rapid and potent inducer of monooxygenase activity and (ii) have a Type II difference Spectrum.(c) 1986 Society of Toxicology


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.