Pharmacology

Original Paper

Pulmonary Metabolism of Imipramine in the Rat and Rabbit

Comparison with Hepatic Metabolism

Ohmiya Y. · Mehendale H.M.

Author affiliations

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Miss., USA

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Pharmacology 1981;22:172–182

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: May 31, 1980
Accepted: June 30, 1980
Published online: May 30, 2008
Issue release date: 1981

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA

Abstract

The pulmonary metabolism of imipramine (IMP) was studied, using lung tissue preparations of rats and rabbits, and compared with the metabolism by liver tissue. The postmitochondrial (9,000 g) supernatant fraction was used as the enzyme source, and the differential extraction method was employed to separate and quantitate the metabolites of IMP. The IMP-metabolizing activity of rat lung was found to be significantly higher than that of rabbit lung. The major metabolite produced by rat lung was identified as IMP-N-oxide (IMP-NO). Inclusion of β-dimethylaminoethyl-diphenyl valerate (SKF-525A; 1 mM) and depletion of Mg2+ did not inhibit, but slightly increased the N-oxidation of IMP by the lung preparations, whereas piperonyl butoxide (1 mM) and Hg2+ (0.1 mM) had little or no effect. The liver/lung ratio of the IMP-metabolizing activity was found to be variable depending on the substrate concentrations used, indicating the unreliability of such ratios as indices of the relative contribution of the lung to the metabolism of a drug. These results suggest that a marked species variation exists with respect to the pulmonary metabolism of IMP, that the principal product in rat lung is IMP-NO, and that this biotransformation is catalyzed by a noncytochrome P-450 pathway.

© 1981 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: May 31, 1980
Accepted: June 30, 1980
Published online: May 30, 2008
Issue release date: 1981

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: https://www.karger.com/PHA


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