Assuntos
Etinilestradiol/isolamento & purificação , Diacetato de Etinodiol/isolamento & purificação , Mestranol/isolamento & purificação , Noretindrona/isolamento & purificação , Noretinodrel/isolamento & purificação , Animais , Radioisótopos de Carbono , Cromatografia Gasosa , Cromatografia por Troca Iônica , Cromatografia em Camada Fina , Cães , Espectrometria de Massas , Noretinodrel/metabolismo , Noretinodrel/urina , Prata , TrítioRESUMO
PIP: Norethynodrel metabolites in human plasma and urine were analyzed. Samples were collected from healthy young women over 1 24-hour period after the oral administration of 11.1 mg (50 mcCi) of 6, 7-tritiated norethynodrel. The 3 alpha-hydroxy compound from the reduction of the 3-ketone of norethynodrel was the major free metabolite in plasma, with lesser amounts of its 3 beta-isomer and norethindrone. These compounds were identified by carrier addition analysis and their concentrations were estimated by thin-layer radiochromatography. The bulk of plasma metabolites consisted of conjugates and greater than 95% of urinary metabolites (20% of total dose) were conjugated; 2 of which were beta-glucuronides. Enzymatic hydrolysis enabled the urinary compounds to be identified by gas-lizuid chromatography-mass spectrometry. 70-80% (10% of the dose) of the enzymatically hydrolyzed urinary metabolites were hydroxylated compounds. Triols were the principal hydroxylated compounds isolated. The metabolism of norethynodrel was rapid and extensive.^ieng
Assuntos
Noretinodrel/metabolismo , Adulto , Cromatografia Gasosa , Cromatografia em Camada Fina , Feminino , Humanos , Hidrólise , Hidroxilação , Cinética , Espectrometria de Massas , Noretinodrel/sangue , Noretinodrel/isolamento & purificação , Noretinodrel/urina , TrítioAssuntos
Anticoncepcionais Orais/metabolismo , Noretinodrel/metabolismo , Adulto , Alcinos/urina , Isótopos de Carbono , Cromatografia , Estranos/urina , Diacetato de Etinodiol/urina , Fezes/análise , Feminino , Meia-Vida , Humanos , Hidroxiesteroides/urina , Noretinodrel/administração & dosagem , Noretinodrel/urina , EstereoisomerismoAssuntos
Anticoncepcionais Orais/metabolismo , Diacetato de Etinodiol/metabolismo , Isótopos de Carbono , Cromatografia Gasosa , Cromatografia em Camada Fina , Diacetato de Etinodiol/administração & dosagem , Diacetato de Etinodiol/síntese química , Fezes/análise , Feminino , Meia-Vida , Humanos , Hidrólise , Raios Infravermelhos , Isomerismo , Espectrometria de Massas , Mestranol/urina , Noretindrona/urina , Noretinodrel/urina , Esteroides/urina , Raios UltravioletaRESUMO
PIP: The in vivo and in vitro metabolism of norethynodrel was studied in detail, and the configuration and conformation of the major metabolites were established. In both the in vivo and in vitro studies, the initial concentration of the ethynyl steroidal fractions was obtained by using silver nitrate-silica gel columns, further purified with alumina chromatography. Only traces of unchanged norethynodrel were found. The major ethynyl steroidal metabolites from in vitro rabbit liver homogenate studies were isolated in pure form and were found to be idential to the product obtained by reducing norethynodrel with sodium borohydride. Through use of proton nuclear magnetic resonance spectra (NMR) and mass spectra studies, the configurations of the major metabolites of both the in vivo and in vitro systems were identified as 17alpha-ethynyl-3alpha, 17beta-dihydroxy-delta-estrene and 17alpha-ethynyl-3beta, 17beta-dihydroxy-delta-estrene. In humans, both compounds are found as the beta-glucosiduronates in the ratio of 7:3 in favor of the 3alphaisomer. The conformation of the 3alpha-hydroxyl group was shown to be equatorial, while that of the 3beta-epimer was axial.^ieng
