| Título: | Metabolism of isorhynchophylline in rats detected by LC-MS |
| Autores: |
Wang, Wei; Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama Ma, Chao-Mei; Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama Hattori, Masao; Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama |
| Fecha: | 2010-02-02 |
| Publicador: | Journal of Pharmacy and Pharmaceutical Sciences |
| Fuente: |
 |
| Tipo: |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| Tema: | No aplica |
| Descripción: | PURPOSE This paper investigates the metabolic fate of isorhynchophylline (ISOR) as a main bioactive oxindole alkaloid in the traditional Chinese medicine. METHODS After oral administration of ISOR to rats, plasma, bile, urine and feces were analyzed by LC-MS. Hydroxylation of ISOR and successive glucuronidation proceeded in vitro by incubation with rat liver microsomes. RESULTS ISOR was identified in plasma, 11-hydroxyisorhynchophylline 11-O--D-glucuronide (MI1) and 10-hydroxyisorhynchophylline 10-O--D-glucuronide (MI2) in bile, and free 11-hydroxyisorhynchophylline (MI3) and 10-hydroxyisorhynchophylline (MI4) in urine and feces. Within 24 h, 71.6% of ISOR was excreted into the feces (in 20.0 g) and 13.8% into the urine (in 20.0 ml) of rats after oral administration of 37.5 mg/kg. Monitoring by LC-MS showed that 8.5% of ISOR was metabolized to MI3 and MI4 in a ratio of ca. 1:1. Specific inhibition of CYP isozymes indicated that CYP2D, CYP1A1/2 and CYP2C participate in ISOR hydroxylation. CONCLUSIONS ISOR was involved in the circulatory system after oral administration. Cytochrome P450 (CYP) in rat liver microsomes played a key role in ISOR hydroxylation. |
| Idioma: | Inglés |
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