RESUMO
PIP: The isolation and identification of the major in vitro metabolites of chlormadinone acetate are reported. Human, rabbit, and rat liver incubations were employed in the isolation and identification, and male rat liver preparations were used to study the effect of phenobarbital stimulation on the formation of these metabolites. The metabolic pathway was influenced by the microsomal stimulating property of phenobarbital. 2alpha-hydroxychlormadinone was the major metabolite from the incubation of phenobarbital-stimulated rabbit and male rat liver. 17alpha-acetoxy-6-chloro-3beta-hydroxypregna-4,6-diene-20-one was the major metabolite from the incubation of unstimulated human and male rat liver. It was concluded that the 2alpha-hydroxychlormadinone acetate was demostrated only as a consequence of phenobarbital treatment.^ieng
Assuntos
Acetato de Clormadinona/metabolismo , Fígado/metabolismo , Acetatos/metabolismo , Acetilação , Idoso , Animais , Biotransformação , Radioisótopos de Carbono , Cromatografia Gasosa , Cromatografia em Camada Fina , Computadores , Feminino , Humanos , Hidroxilação , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Microssomos Hepáticos/metabolismo , Pessoa de Meia-Idade , Oxirredução , Fenobarbital/farmacologia , Coelhos , Ratos , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
PIP: Tracing the metabolic fate of steroidal antifertility agents is assisted by radioactive labelling. Chlormadinone-4-14C acetate was synthesized, and the reaction sequences are reviewed. The overall yield was moderate (12-16%) but the compound was radiochemically and spectrophotometrically pure. The chemical compounds, structures, and reactions are described in detail.^ieng
Assuntos
Acetato de Clormadinona , Anticoncepção , Anticoncepcionais , Anticoncepcionais Femininos , Serviços de Planejamento FamiliarAssuntos
Anormalidades Induzidas por Medicamentos , Noretinodrel/efeitos adversos , Administração Oral , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Criptorquidismo/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Hidrocefalia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos , Osso Parietal/anormalidades , GravidezAssuntos
Pentobarbital/urina , Animais , Barbitúricos/análise , Cromatografia , Cães , Feminino , Dispersão Óptica RotatóriaAssuntos
Noretinodrel/farmacologia , Reprodução/efeitos dos fármacos , Animais , Corpo Lúteo/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Feminino , Fertilização/efeitos dos fármacos , Feto/efeitos dos fármacos , Noretinodrel/metabolismo , Ovulação/efeitos dos fármacos , Gravidez/efeitos dos fármacos , RatosRESUMO
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