RESUMEN
Studies on the Metabolic Fate of [14C]2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in the Mouse. KOSHAKJI, R. P., HARBISON, R. D., and BUSH, M. T. (1984). Toxicol. Appl. Pharmacol. 73, 69-77. After a single po dose (135 micrograms/kg; 62 microCi/kg) of 14C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male ICR/Ha Swiss mice, 67 to 76% of the administered dose was eliminated via the feces and 1 to 2% in the urine during the first 24 hr following treatment. It seems likely that most of this material was simply not absorbed. Much of the remaining chemical was then excreted slowly in the urine (2%) and feces (7%) during the next 10 days, partly as the unchanged compound and partly as metabolites. One of the metabolites (Fraction II) appears to be a single polar, acidic metabolite characterized in urine (0.4 +/- 0.1%) and feces (2.2 +/- 0.2%), and is also likely excreted as a glucuronide conjugate. The rest of the radioactivity was in the form of unchanged TCDD in the animal body (17 +/- 2%). Steady rates of decline in the concentrations of the 14C as well as of the unchanged TCDD were reached in the feces and urine after the fifth day following the administration of the chemical. Based on this steady rate, the half-life of the radioactivity in the body was approximately 20 days. Urine, feces, and whole body were analyzed by solvent extraction, 14C counting, thin-layer chromatography, and countercurrent distribution.
Asunto(s)
Dioxinas/metabolismo , Dibenzodioxinas Policloradas/metabolismo , Animales , Radioisótopos de Carbono , Cromatografía en Capa Delgada , Distribución en Contracorriente , Heces/análisis , Hidrólisis , Marcaje Isotópico , Masculino , Ratones , Ratones Endogámicos ICR , Dibenzodioxinas Policloradas/orinaAsunto(s)
Preparaciones Farmacéuticas/aislamiento & purificación , Bioensayo , Fenómenos Químicos , Química , Técnicas de Química Analítica/instrumentación , Concentración de Iones de Hidrógeno , Matemática , Métodos , Preparaciones Farmacéuticas/metabolismo , Técnica de Dilución de Radioisótopos , Radioisótopos , SolventesRESUMEN
Pregnant mice were treated with a single oral dose of [carboxy-14C]2,4,5-T (100 mg/kg; 1.22 mu Ci/mg) on day 12 of gestation and sacrificed after 0.25, 0.5, 2 and 24 hours. Maternal blood, embryos, placentas and yolk sacs were analyzed by solvent extraction, TLC, and countercurrent distribution. Expressed as percentage of the administered dose/g tissue, the unchanged 2,4,5-T found in maternal blood, placentas, yolk sacs, and embryos was 3, 0.5, 0.5, and 0.2%, respectively, after 0.25 hours, and 4, 2, 2, and 0.5%, respectively, after 24 hours. No major metabolites of 2,4,5-T were detected. Urine and feces were also collected and analyzed. Radioactivity was largely eliminated in the urine, 69-78% of the administered dose in 7 days. Feces contained 5-9% of the dose. In the urine unchanged 2,4,5-T accounted for 35-44% of the dose, and 22-23% as very polar material. Unchanged 2,4,5-T in the feces was 3-5% and 1-2% as polar material. 2,4,5-T administered to pregnant mice is largely distributed and eliminated as 2,4,5-T and very polar material.
Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/metabolismo , Embrión de Mamíferos/metabolismo , Placenta/metabolismo , Preñez , Saco Vitelino/metabolismo , Ácido 2,4,5-Triclorofenoxiacético/sangre , Ácido 2,4,5-Triclorofenoxiacético/orina , Animales , Cromatografía en Capa Delgada , Distribución en Contracorriente , Heces/análisis , Femenino , Cinética , Ratones , EmbarazoRESUMEN
The metabolism of 14C-triamterene (TA), 2,4,7-triamino-6-phenylpteridine, was investigated in rats. After administration of 14C-TA (2 mg/kg, sc), 45% and 50% of the total radioactivity was excreted in urine and feces, respectively, during 72 hr. 14C-TA and its metabolites were separated by paper chromatography and countercurrent distribution. Unchanged TA in the urine and feces accounted for 72-79% of the dose. The major metabolites in the excreted dose were free p-hydroxytriamterene (10-15%) and its conjugate (1-5%). Three hours after administration of the drug, the major metabolites were not found in gastrointestinal contents or urine when the bile duct was cannulated. They were formed in the liver and secreted in bile. A minor unidentified metabolite (2% of the dose) was also formed in the liver and excreted in urine and feces.
Asunto(s)
Triantereno/metabolismo , Animales , Bilis/metabolismo , Cromatografía en Papel , Distribución en Contracorriente , Sistema Digestivo/metabolismo , Heces/análisis , Hidroxilación , Técnicas In Vitro , Hígado/metabolismo , Masculino , Ratas , Factores de Tiempo , Triantereno/orinaRESUMEN
The metabolism of the anticonvulsant drug primidone (PRM) was studied in the isolated perfused rat liver by a radiotracer methodology that permits nearly quantitative accounting of the dose as drug and identified metabolites. 14C-PRM and its metabolites were separated by thin-layer chromotography and quantitated by liquid-scintillation counting PRM was extensively converted to known active metabolites: phenobarbital (PB), 15%, and phenylethylmalonamide, 80%, in control livers during 120 minutes. Pretreatment of rats with PB greatly accelerated the rate of PRM metabolism, pretreatment with PRM only moderately so. There was no differential induction of the two metabolism pathways. Addition of phenylethylmalonamide to the perfusate reduced the rate of PRM metabolism but addition of PB did not. It is concluded that conversion of PRM to its active metabolites may be simultaneously influenced by the processes of metabolite induction (PB) and metabolite inhibition (phenylethylmalonamide).
Asunto(s)
Hígado/metabolismo , Primidona/metabolismo , Radiometría/métodos , Animales , Bilis/análisis , Radioisótopos de Carbono , Cromatografía en Capa Delgada , Relación Dosis-Respuesta a Droga , Hígado/análisis , Masculino , Perfusión , Fenobarbital/farmacología , Feniletilmalonamida/administración & dosificación , Feniletilmalonamida/farmacología , Primidona/farmacología , Ratas , Espectrofotometría Ultravioleta , Factores de TiempoRESUMEN
The use of the ethnoscientific method in nursing research is demonstrated in an initial study and a replication of that study, utilizing male and female informants. The domain of "mental health" was explored, analyzed, and contrasted within the subculture of the central city resident and the subculture of the psychiatric-mental health professional. To facilitate an understanding of ethnoscience, the method is briefly outlined; then, to illustrate the methodology, data from one informat are presented in depth. A summary of the major similarities and contrasts that emerged from the data of both studies is presented. Implications for nursing of the research and ethnoscience are discussed.
Asunto(s)
Cultura , Salud Mental , Semántica , Adulto , Antropología Cultural , Servicios Comunitarios de Salud Mental , Etnopsicología , Familia , Femenino , Felicidad , Humanos , Relaciones Interpersonales , Masculino , Trastornos Mentales , Solución de Problemas , Psiquiatría , Asistencia Pública , Religión y Psicología , Factores Sexuales , Población Urbana , Washingtón , Trabajo , Recursos HumanosRESUMEN
The disposition of phenobarbital (PB) was studied in normal individuals and in patients with cirrhosis or acute viral hepatitis to determine 1) if there is significant impairment of PB metabolism in hepatic disease and 2) to what extent such abnormal disposition of the drug affects its disappearance from blood. The diagnosis of liver disease was based on characteristic clinical findings, biochemical liver "function" tests and liver biopsy when necessary. All individuals had normal renal function and were free of other drug and alcohol intake for at least 3 weeks. With radiotracer methodology, PB and its principal metabolites, p-hydroxyphenobarbital (PBOH) and conjugated PBOH (PBOC), were monitored in blood and urine for 5 days after a single dose of 14-C-PBadministered intraduodenally. PB blood half-life (T1/2) in the control group was 86 plus or minus 3 hours (S.E.). In cirrhotics the T1/2 was prolonged to 130 plus or minus 15 hours (P less than .001) and this was accompanied by a 50% reduction in urinary PBOC excretion (P less than .05). Urinary excretion of PB and PBOH was unaltered by cirrhosis. In patients with acute viral hepatitis, PB T1/2 was not significantly prolonged and urinary excretion of PB and its metabolites was in the normal range (P greater than .05). No PBOH and only traces of PBOC were detected in the blood of either control individuals or patients with liver disease. Urinary excretion of unchanged PB was an important elimination pathway of the drug in all groups. As a result of this, PB T1/2 in cirrhosis was only moderately prolonged.