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M T Bush

Publications and source records attributed to M T Bush.

At least 19 recordsLinked to original sources
PubMed1984

Studies on the metabolic fate of [14C]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse.

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.

Animals↗
PubMed1979

Metabolism and distribution of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in pregnant mice.

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.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1975

Study of the hepatic metabolism of primidone by improved methodology.

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).

Animals↗
PubMed1975

The effect of liver disease in man on the disposition of phenobarbital.

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.

Adult↗