RESUMO
A direct gas chromatographic method for unstable amino ketones, using a neutral column and moderately alkaline conditions during extraction has been developed. Its application has given a new perspective to the relative importance of the metabolic routes in the complex metabolism of diethylpropion which after oral administration in man is rapid and extensive (only 3-4% of the drug remains unchanged). Mono-N-de-ethylation is the main pathway (about 35% of the dose). N-De-ethylation is more important than carbonyl-reduction, occurring mainly with the unchanged drug (about 20% of the dose). Norephedrine, thought previously to be one of the main metabolites, has been shown to be present only in negligible amounts. About 30% of the dose, which cannot be accounted for as the sum of the amines recovered in urine, is probably metabolized by deamination, followed by oxidation and conjugation to give hippuric acid.
Assuntos
Dietilpropiona/metabolismo , Biotransformação , Cromatografia Gasosa , Preparações de Ação Retardada , Dietilpropiona/administração & dosagem , Dietilpropiona/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , Cinética , Masculino , ComprimidosRESUMO
Sensitive and specific procedures based on gas liquid chromatography for the identification, separation and determination of amfepramon (diethylpropion) and its major metabolites ethylaminopropiophenone and diethylnorpseudoephedrine in human plasma, saliva and urine have been described. Acidification of the biological fluid samples has improved the stability of the compounds under conditions of storage.
Assuntos
Líquidos Corporais/análise , Dietilpropiona/análise , Biotransformação , Cromatografia Gasosa , Dietilpropiona/sangue , Dietilpropiona/urina , Estabilidade de Medicamentos , Humanos , Saliva/análiseRESUMO
The absorption of diethylpropion (DEP I), dimethylpropion (DMP I) and some of their basic metabolites into and passage through the skin was investigated and a comparison of their metabolism following oral and percutaneous administration made. High percentages (60-80%) of DEP I and its metabolites and a small percentage of DMP I and its metabolites were taken up into the skin in less than 2 min--the remaining percentages of the compounds were absorbed into the skin by a first order process. The rate of appearance of the compounds in the blood, which reflects their rate of passage through the skin, did not correlated with their rate of absorption into the skin. More metabolism occurred with all the compounds after their oral administration than after their percutaneous application.
