Asunto(s)
Azidas/metabolismo , Citratos/farmacología , Cimarina/metabolismo , Isoenzimas/biosíntesis , Retina/enzimología , ATPasa Intercambiadora de Sodio-Potasio/biosíntesis , Estrofantinas/metabolismo , Animales , Cimarina/análogos & derivados , Inducción Enzimática , Masculino , Metionina/metabolismo , Ratas , Ratas Endogámicas , Valores de ReferenciaRESUMEN
In 33 healthy male volunteers, given a single oral and intravenous dose of cymarin (k-strophanthin-alpha), k-strophanthoside (k-strophanthin-gamma) and ouabain (g-strophanthin), enteral absorption and renal excretion of these glycosides and their metabolites were investigated by radioimmunoassay and HPLC. Cymarin was absorbed at 47% of the given dose. After intravenous injection 46% and after oral administration 21% of the given dose, i.e. the total amount as detected by radioimmunoassay which consisted of the unchanged glycoside and its metabolites, were excreted by the kidneys mainly as conjugated metabolites. The half-life of elimination, calculated from the total excreted amount was 13 h (i.v.) and 23 h (p.o.), respectively. k-Strophanthoside was absorbed at 16% of the given dose. After i.v.-injection 73% of the given dose was excreted by the kidneys with a half-life of elimination of 99 h. From this total amount about 70% was excreted as the unchanged drug, the remaining 30% as various metabolites. After oral administration 11% of the given dose were excreted with a half-life of elimination of 22 h. 80% of this amount consisted mainly of conjugated k-strophanthoside and conjugated metabolites as k-strophanthin-beta, cymarin, k-strophanthidin, cymarol and k-strophanthidol. Only 6% was excreted as the unchanged drug. Ouabain was absorbed after oral administration to a minimum of 1.4%. Given intravenously a total renal excretion of 33% of the given dose with a half-life of elimination of 23 h was measured. Of this 80% was unchanged ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Estrofantinas/metabolismo , Administración Oral , Adulto , Biotransformación , Cimarina/metabolismo , Humanos , Inyecciones Intravenosas , Absorción Intestinal , Masculino , Ouabaína/metabolismo , Estrofantinas/orinaRESUMEN
In 10 patients, 5 having received 3H-cymarol i.v., 5 orally, the radioactivity in plasma, urine and in the feces of some patients also was determined. After oral administration the plasma levels rose rapidly reaching maximum levels 1--2 h after administration. After i.v. injection about 30% of the given radioactivity were excreted in the urine. The remaining radioactivity was found in the feces suggesting a high biliary excretion. Only 10% of the radioactivity excreted in the first 24 h were chloroform-extractable. The radioactivity found in the urine after oral administration of the drug amounted to 17.6%. Between 51.1 and 58.5% of the drug were bound to serum proteins.
Asunto(s)
Cimarina/metabolismo , Estrofantinas/metabolismo , Anciano , Proteínas Sanguíneas/metabolismo , Cimarina/análogos & derivados , Cimarina/sangre , Cimarina/orina , Heces/análisis , Humanos , Absorción Intestinal , Masculino , Persona de Mediana Edad , Unión ProteicaRESUMEN
1. Diacetylcymarol is an acetylated glycoside which is better absorbed than the parent glycoside, cymarol. 2. Diacetyl[19-3H]cymarol was rapidly metabolized and excreted by the rat following intraperitoneal administration. 3. The drug was metabolized extensively to polar compounds with the principal pathway involving loss of the C-19 acetyl group and probable demethylation of the sugar. 4. The bulk of the radioactive material was excreted in the bile and there was little reabsorption. 5. The results show that acetylation was successful in converting the poorly absorbed glycoside, cymarol, into a derivative that was rapidly absorbed from the peritoneal cavity. 6. Following or during absorption, the biologically inactive diacetylcymarol was converted to polar derivatives with potential therapeutic activity. However, subsequent elimination was so rapid that little therapeutic benefit could be expected.