Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats |
| |
Authors: | W Daniel K J Netter |
| |
Institution: | (1) Department of Pharmacology and Toxicology, University of Marburg, Medical School, Lahnberge, D-3550 Marburg (Lahn), Federal Republic of Germany;(2) Present address: Institute of Pharmacology, Department of Biochemistry, Polish Academy of Sciences, Smetna 12, P-31-343 Krakow, Poland |
| |
Abstract: | Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome.
Send offprint requests to K. J. Netter |
| |
Keywords: | Imipramine Carbamazepine Pharmacokinetic interaction Cytochrome P 450 concentration Substrate binding Blood levels In vitro imipramine demethylation and hydroxylation |
本文献已被 SpringerLink 等数据库收录! |
|