Assuntos
Preparações Farmacêuticas/metabolismo , Especificidade da Espécie , Acetamidas/metabolismo , Animais , Anti-Inflamatórios/sangue , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Carcinógenos/metabolismo , Gatos , Cricetinae , Ácidos Cicloexanocarboxílicos/sangue , Ácidos Cicloexanocarboxílicos/toxicidade , Cães , Fluorenos/metabolismo , Cobaias , Meia-Vida , Haplorrinos , Humanos , Hidroxilação , Indóis/sangue , Indóis/toxicidade , Inseticidas/metabolismo , Cinética , Camundongos , Hipófise/metabolismo , Coelhos , Ratos , Roedores , OvinosAssuntos
Anticonvulsivantes/farmacologia , Diazepam/metabolismo , Diazepam/farmacologia , Tecido Adiposo/metabolismo , Animais , Anticonvulsivantes/análise , Anticonvulsivantes/metabolismo , Benzazepinas/metabolismo , Encéfalo/metabolismo , Química Encefálica , Fenômenos Químicos , Química , Diazepam/análise , Diazepam/sangue , Feminino , Masculino , Camundongos , Músculos/análise , Músculos/metabolismo , Miocárdio/metabolismo , Oxazepam/metabolismo , Pentilenotetrazol , Convulsões/induzido quimicamente , Fatores de Tempo , TrítioAssuntos
Anticonvulsivantes/metabolismo , Anticonvulsivantes/farmacologia , Clordiazepóxido/metabolismo , Clordiazepóxido/farmacologia , Animais , Encéfalo/metabolismo , Isótopos de Carbono , Clordiazepóxido/sangue , Cromatografia em Camada Fina , Antagonismo de Drogas , Fluorometria , Camundongos , Músculos/metabolismo , Pentilenotetrazol/farmacologia , Fatores de TempoAssuntos
Bilirrubina/sangue , Ligação Proteica/efeitos dos fármacos , Benzoatos/farmacologia , Sítios de Ligação , Eletroforese das Proteínas Sanguíneas , Proteínas Sanguíneas/metabolismo , Humanos , Métodos , Salicilatos/farmacologia , Albumina Sérica/metabolismo , Espectrofotometria Ultravioleta , Sulfadimetoxina/farmacologia , Sulfisoxazol/farmacologia , Desacopladores/farmacologiaRESUMO
Previous studies with 9000g supernatant fractions of rat liver revealed that the 1,4-benzodiazepine, medazepam, was converted to N-desmethyldiazepam by a series of reactions including hydroxylation, N-demethylation, and dehydrogenation. The present study was designed to determine if the pathway via diazepam as intermediate, which is one of three possible pathways, is the major route in vivo in the rat for N-desmethyldiazepam formation from medazepam. Measurement of the levels of labeled drug and metabolites in blood, brain, lung, heart, and muscle 5 min after the oral administration of approximately equivalent doses of [14C]medazepam hydrochloride, [14C]diazepam, or N-desmethyl[14C]medazepam revealed that each drug was both rapidly absorbed and oxidatively metabolized in the rat. At 1 hr. the tissue levels of labeled N-desmethyldiazepam were highest after N-desmethyl-[14C]medazepam, intermediate after [14C]medazepam hydrochloride and lowest after [14C]diazepam. These results indicated that in the formation of N-desmethyldiazepam from medazepam in the rat there is a substantial preference for the pathway via N-desmethylmedazepam over that in which diazepam is an intermediate. From consideration of the limited data available, it is suggested that this same preference in pathways may also hold true in humans.