Investigations on the metabolic pathways of cyclosporine: II. Elucidation of the metabolic pathways in vitro by human liver microsomes
| Autor: | Uwe Christians, R. Kownatzki, S. Strohmeyer, Hans-Martin Schiebel, Schottmann R, K F Sewing, Jörg S. Bleck, K. Kohlhaw |
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| Rok vydání: | 1991 |
| Předmět: |
Pharmacology
biology Human liver Health Toxicology and Mutagenesis Metabolite General Medicine Metabolism In Vitro Techniques Toxicology biology.organism_classification Mass spectrometry Biochemistry Mass Spectrometry In vitro chemistry.chemical_compound Metabolic pathway chemistry Microsoma Cyclosporine Microsomes Liver Microsome Bile Humans Chromatography High Pressure Liquid |
| Zdroj: | Xenobiotica. 21:1199-1210 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.3109/00498259109039560 |
| Popis: | 1. Cyclosporine and its metabolites, isolated from human bile and identified by FAB mass spectrometry and 1H-n.m.r. spectroscopy, were metabolized by human liver microsomes for the identification of new cyclosporine metabolites. From these data a metabolic pathway for cyclosporine, which includes these new cyclosporine metabolites, has been proposed. The new metabolites were isolated by semi-preparative h.p.l.c. and their chemical structures were elucidated by FAB mass spectrometry. These isolated metabolites were further metabolized and the products identified by FAB mass spectrometry. 2. Fourteen metabolites, whose structure has not yet been elucidated, were isolated after metabolism of structurally identified cyclosporine metabolites, and chemical structures for five of these metabolites were proposed. 3. The structures of the new cyclosporine metabolites were: (i) a N-demethylated, carboxylated derivative (AM1A4N), (ii) a di-hydroxylated, N-demethylated derivative (AM14N9), (iii) a hydroxylated and carboxylated derivative (AM1A9), (iv) a di-hydroxylated, cyclized and N-demethylated derivative (AM1c4N9) and (v) a cyclized and carboxylated (AM1cA) derivative. 4. A proposed cyclosporine metabolic pathway comprises a total of 29 metabolites. It consists of four main branches originating from metabolites AM1, AM1c, AM9 and AM4N. |
| Databáze: | OpenAIRE |
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