RESUMEN
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%.
Asunto(s)
Bencimidazoles/farmacología , Bencimidazoles/farmacocinética , Morfolinas/farmacología , Morfolinas/farmacocinética , Administración Oral , Animales , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Masculino , RatasRESUMEN
Pharmacokinetic parameters of himantane and its metabolites in the blood plasma of rabbits were compared after single administration of himantane solution in a dose of 25 mg intravenously and 100 mg orally. It was established that the original substance is characterized by low absolute bioavailability (7.95%). Himantane is subjected to first-pass effect and is extensively metabolized in the liver to metabolites with m/z 266 and 250.
Asunto(s)
Adamantano/análogos & derivados , Adamantano/administración & dosificación , Adamantano/sangre , Adamantano/metabolismo , Adamantano/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Estudios Cruzados , Inyecciones Intravenosas , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , ConejosRESUMEN
The pharmacokinetics ofhemantane after administration in different ways has been studied in rats. It is established that hemantane introduced both orally (p.o.) and intravenously (i.v.) is very intensively metabolized, with the main metabolites characterized by m/z = 250 and 266 and detected for 6 hours after the administration in both ways. Hemantane shows high rate of permeability into its target organ--brain--whereas the permeation of its metabolites is extremely low. The absolute bioavailability ofhemantane upon p.o. administration was 14.1%. The substance is subject to the "first-pass effect". The unchanged substance was determined in daily urine and feces in very small fractions of the administered dose: 0.23% in urine and 0.08% in feces after i.v. administration and 0.02% in feces after p.o. administration. Thus, it may be concluded that the substance is completely absorbed in rats from the gastro-intestinal tract into systemic blood circulation.
Asunto(s)
Adamantano/análogos & derivados , Antiparkinsonianos/farmacocinética , Enfermedad de Parkinson/tratamiento farmacológico , Adamantano/administración & dosificación , Adamantano/sangre , Adamantano/farmacocinética , Adamantano/orina , Animales , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/sangre , Antiparkinsonianos/orina , Disponibilidad Biológica , Biotransformación , Química Encefálica , Cromatografía Liquida , Heces/química , Humanos , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Masculino , Ratas , Ratas Endogámicas , Espectrometría de Masas en Tándem , Distribución TisularRESUMEN
The formula of a new stable 20% benzylbenzoate emulsion is presented, so are the results of studies on its toxicity, local irritating and sensitizing effects in guinea pigs. For comparison, the same characteristics of currently used 20% water-soap benzylbenzoate emulsion and of the new ointment base, SAKAP (acryl copolymer), have been examined. Both the ointment and its base have proved to be safe.
