Stimulation of caffeine metabolism in the rat by 3-methylcholanthrene |
| |
Authors: | Andrew Aldridge William D. Parsons Allen H. Neims |
| |
Affiliation: | McGill University, Department of Pharmacology & Therapeutics, Roche Developmental Pharmacology Unit, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec H3G 1Y6, Canada |
| |
Abstract: | Groups of adult male rats treated with 3-methylcholanthrene, phenobarbital or vehicles alone, were administered caffeine either orally or intravenously. Serum caffeine concentrations were measured by radioimmunoassay. In vehicle and phenobarbital pretreated animals, caffeine elimination kinetics were non-linear. In control animals, the apparent Km was 8 μg·ml?1 (40 μM) and the apparent Vmax was 0.1 μg·ml?1·min?1 (0.5 μM·min?1). Phenobarbital pretreatment did not change the apparent Km but slightly increased the apparent Vmax. 3-Methylcholanthrene pretreatment dramatically altered the elimination kinetics of caffeine, whether caffeine was given orally or intravenously. The elimination of caffeine from serum of 3-methylcholanthrene pretreated rats was first order with a of approximately 14 minutes.Our results are consistent with the proposed involvement of the cytochromes P-450 monooxygenase system in the elimination of caffeine. In addition, our results suggest that caffeine is a moderately poor substrate for the cytochromes P-450 present in control and phenobarbital-pretreated rats, but a particularly good substrate for the form(s) induced by 3-methylcholanthrene. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|