RESUMO
The main pharmacokinetic parameters (AUC0-∞, Tmax, Cmax, Cl/F, t1/2 el, MRT, Cmax/AUC0-I, Vd/F) of afobazole base in a new pharmaceutical composition and afobazole dihydrochloride substance after single peroral administration have been determined in rats. The availability of afobazole base pharmaceutical composition relative to that of the substance amounted to 153.2%.
Assuntos
Benzimidazóis/farmacologia , Benzimidazóis/farmacocinética , Morfolinas/farmacologia , Morfolinas/farmacocinética , Administração Oral , Animais , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Masculino , RatosRESUMO
The excretion of compound M-11 and its metabolites with the urine and feces was studied in rats after intraperitoneal and oral administration in a dose of 25 mg/kg. Experiments showed that 1% metabolites were detected in excretions over 24 h irrespective of the route of administration, while the initial compound was not found even in trace amounts.
Assuntos
Benzimidazóis/análise , Benzimidazóis/metabolismo , Benzimidazóis/farmacocinética , Fezes/química , Morfolinas/análise , Morfolinas/metabolismo , Morfolinas/farmacocinética , Administração Oral , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/urina , Biotransformação , Cromatografia Líquida de Alta Pressão , Injeções Intraperitoneais , Masculino , Estrutura Molecular , Morfolinas/administração & dosagem , Morfolinas/urina , Ratos , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
Comparative analysis of pharmacokinetic parameters of afobazole and its main metabolite M-11 after single intraperitoneal injections of their solutions (25 mg/kg) to rats showed much more intense penetration of M-11 compared to afobazole into rat tissues and organs, judging from the area under the pharmacokinetic curve (AUC) and maximum concentrations (C(max)). The half-life periods (T(l/2e)l) of afobazole and M-11 were similar.
Assuntos
Ansiolíticos/farmacocinética , Benzimidazóis/farmacocinética , Morfolinas/farmacocinética , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/metabolismo , Área Sob a Curva , Benzimidazóis/administração & dosagem , Benzimidazóis/metabolismo , Cromatografia Líquida de Alta Pressão , Meia-Vida , Injeções Intraperitoneais , Masculino , Morfolinas/administração & dosagem , Morfolinas/metabolismo , RatosRESUMO
The amount of afobazole and identified metabolites was measured in the urine and feces of rats after intraperitoneal and peroral administration of the drug in a dose of 25 mg/kg. Over 1 day after intraperitoneal or peroral treatment with afobazole, urine and feces contained 0.1% initial compound (from administered dose) and 42.1% metabolites.
Assuntos
Benzimidazóis/farmacocinética , Benzimidazóis/urina , Fezes/química , Morfolinas/farmacocinética , Morfolinas/urina , Animais , Animais não Endogâmicos , Ansiolíticos/sangue , Ansiolíticos/metabolismo , Ansiolíticos/farmacocinética , Ansiolíticos/urina , Benzimidazóis/sangue , Benzimidazóis/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Masculino , Morfolinas/sangue , Morfolinas/metabolismo , Ratos , Fatores de TempoRESUMO
Intraperitoneally injected afobazole and its major metabolites are intensively distributed in highly vascularized tissues of rats, including the liver, spleen, and kidneys; the content of these compounds in moderately and poorly vascularized tissues (muscles and mesentery) is much lower. Afobazole and its metabolites possess intermediate ability to penetrate into the brain.
