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Int J Clin Exp Pathol ; 8(5): 5584-90, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26191268

RESUMEN

Vorinostat (suberoylanilide hydroxamic acid, SAHA) is the first approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma after progressive disease following two systemic therapies. The rats were randomly divided into SAHA groups (low, medium and high dosage) and control group. The SAHA group rats were given 12.3, 24.5, and 49 mg/kg SAHA, respectively, by continuous intragastric administration for 7 days. The influence of SAHA on the activities of CYP450 isoforms CYP2B6, CYP1A2, CYP2C19, CYP2D6 and CYP2C9 were evaluated by cocktail method, they were responsed by the changes of pharmacokinetic parameters of bupropion, phenacetin, tolbutamide, metroprolol and omeprazole. The five probe drugs were given to rats through intragastric administration, and the plasma concentration were determined by UPLC-MS/MS. The result of SAHA group compared to control group, there were statistical pharmacokinetics difference for bupropion, phenacetin, tolbutamide and metroprolol. Continuous intragastric administration for 7 days may induce the activities of CYP2C19 of rats, inhibit CYP1A2 and slightly inhibit CYP2B6 and CYP2D6 of rats. This may give advising for reasonable drug use after co-used with SAHA. The results indicated that drug co-administrated with SAHA may need dose adjustment. Furthermore, continuous intragastric administration of SAHA for 7 days, liver cell damaged, causing liver cell edema, in liver metabolism process.


Asunto(s)
Inhibidores del Citocromo P-450 CYP1A2/administración & dosificación , Inductores del Citocromo P-450 CYP2C19/administración & dosificación , Citocromo P-450 CYP2C19/biosíntesis , Citocromos/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/administración & dosificación , Ácidos Hidroxámicos/administración & dosificación , Hígado/efectos de los fármacos , Administración Oral , Animales , Bupropión/sangre , Bupropión/farmacocinética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Cromatografía Liquida , Citocromo P-450 CYP1A2 , Inhibidores del Citocromo P-450 CYP1A2/toxicidad , Citocromo P-450 CYP2B6/metabolismo , Inhibidores del Citocromo P-450 CYP2B6/administración & dosificación , Inductores del Citocromo P-450 CYP2C19/toxicidad , Citocromo P-450 CYP2D6/metabolismo , Inhibidores del Citocromo P-450 CYP2D6/administración & dosificación , Citocromos/metabolismo , Interacciones Farmacológicas , Edema/inducido químicamente , Edema/patología , Inducción Enzimática , Inhibidores de Histona Desacetilasas/toxicidad , Ácidos Hidroxámicos/toxicidad , Hígado/enzimología , Hígado/patología , Masculino , Metoprolol/sangre , Metoprolol/farmacocinética , Omeprazol/sangre , Omeprazol/farmacocinética , Fenacetina/sangre , Fenacetina/farmacocinética , Ratas Sprague-Dawley , Especificidad por Sustrato , Espectrometría de Masas en Tándem , Tolbutamida/sangre , Tolbutamida/farmacocinética , Vorinostat
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