Maximum Levels Of Radioactivity Research Articles

Metabolic Fate of a New Dihydropyridine Calcium Antagonist, AE0047. (III): Placental Transfer and Milk Transfer of 14C-AE0047.

The transfer of radioactivity to fetus and milk were studied in the pregnant or lactating rats after a single oral administration of 14C-AE0047 at the dose of 3 mg/kg. The localization of the radioactivity was visualized by whole body autoradioluminography and was determined by the excised tissue-liquid scintillation method. 1. When 14C-AE0047 was administered orally at a dose of 3 mg/kg to pregnant rats (19th day of gestation), the maximum levels of radioactivity in the fetus were observed at 6 hr after the administration and accounted for 6.0% of the Cmax present in the maternal plasma. The amounts of radioactivity transferred to one fetus was 0.009 to 0.015% of administered dose. 2. When 14C-AE0047 was administered orally at a dose of 3 mg/kg to lactating rats (the 19th day after delivery), the maximum level in milk was reached at 6 hr and it was lower than that in the maternal plasma.

Placental Transfer and Mammary Excretion of 1-(Bis(4-fluorophenyl)-methyl)-4-(2,3,4-trimethoxybenzyl)piperazine Dihydrochloride(KB-2796) in Rats.

The placental transfer and mammary excretion of 1-[bis(4-fluorophenyl)-methyl]-4-(2, 3, 4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796) were studied in rats after oral administration of 14C-labeled KB-2796. 1. The whole-body autoradiograms after oral administration to rats on the 13th day of pregnancy showed that the radioactivity in the fetus was higher than that in the placenta. 2. The maximum levels of radioactivity in the fetus were reached at 1 hr after administration to rats on the 18th day of pregnancy. The elimination of radioactivity in the fetus was slower than that in maternal plasma. The levels of radioactivity in the fetus at 48 hr was about 4 times higher than that in the mater nal plasma. In the fetus, radioactivity in the liver and lung was relatively higher than in other tissues, and the radioactivity in the lung was increasing up to 96 hr after the administration. 3. The maximum levels of radioactivity in the milk reached at 6 hr after the administration to lactating rats. The concentration is 37 times higher than that in the plasma. Thereafter, the concentration in the milk declined with half-life of 12.3 hr by 48 hr after dosing. The elimination was parallel to the plasma level. 4. The main metabolites of KB-2796 in the maternal and fetal lung were bis(4-fluorophenyl)methylpiperazine (M6) and 4, 4'-difluorobenzophenone (M10). 5. The unchanged KB-2796 accounted for about 60% of total radioactivity in the milk. 1-[Bis (4-fluorophenyl) methyl]-4-(3, 4-dimethoxy-2-hydroxybenzyl) piperazine (M2) and M10 were detected as the main metabolites in the milk.

Studies on the Metabolic Fate of Semotiadil Fumarate (SD-3211) I: Absorption, Distribution, Metabolism and Excretion after Single Administration to Male Rats.

The absorption, distribution, metabolism and excretion of 14C-semotiadil fumarate (14C-SD3211) were studied in rats after oral (dose ; 10mg/kg) or intravenous (1 mg/kg) single administration. 1. Concentration of radioactivity in the plasma reached the maximum level of 0.26μg/ml at 1 hr after oral administration and decreased with the half-life of 6.4hr. Concentration of SD-3211 in the plasma reached the maximum level of 0.13μg/ml at lhr, and decreased with the half-life of 3.5hr. 2. Maximum levels of radioactivity in most of tissues were reached at 2 ?? 6hr after oral administration, and high levels of radioactivity were observed in the liver, lung, kidney and harderian gland. At 96hr after oral administration, the levels in every tissue were very low compared with the maximum level. 3. Within 96hr, excretion of radioactivity was about 1.2% and 93.8% of the dose in urine and feces after oral administration, respectively. Similar excretion pattern was observed after intravenous administration, where 5.6% and 93.0% of the dose was excreted to urine and feces. 4. Within 48hr, biliary excretion of radioactivity was 87.3% of the dose after oral administration, and was 88.6% after intravenous administration. 5. In the plasma, lung and kidney, unchanged form was found about 37 ?? 58%, within 6hr after oral administration. But, in liver, unchanged form was minor component. In urine, feces and bile, unchanged form were scarcely detected.

Metabolic fate of the new .BETA.-adrenoceptor antagonist, bisoprolol, in animals (1): Absorption, distribution and excretion of 14C-bisoprolol in rats.

The absorption, distribution and excretion of bisoprolol were studied in rats after oral or intravenous administration of 14C-bisoprolol (1 mg/kg). 1. 14C-Bisoprolol was readily and almost completely absorbed from the gastrointestinal tract.2. Following oral administration, serum levels of radioactivity reached a maximum at 1 hr, and declined relatively rapidly with a half-life of 1.2 hr.3. Maximum levels of radioactivity in most tissues were reached within 1 hr after oral administration, and high levels of radioactivity were observed in the liver, kidney and lung. At 24 hr, slight radioactivity was found only in the excretory organs.4. Excretion of radioactivity was 70-80 % and 15-25 % of the dose in urine and feces, respectively, within 72 hr in either route of drug administration. No sex difference was observed in excretion of radioactivity.5. Biliary excretion of radioactivity was 22-26 % of the dose irrespective of dosage route, and partial reabsorption of biliary excreta occurred from the intestinal tract.6. The extent of in vitro binding of 14C-bisoprolol to plasma proteins of various animal species was 18-23 % in rats, rabbits and dogs, while that in human was about 40 %. The binding of bisoprolol to human plasma proteins was not affected by other co-administered drugs. In the in vivo experiment, the percent binding of 14C-bisoprolol and/or its radioactive metabolites to the rat plasma protein was about 17 % after the intravenous dose and about 8 % after the oral dose.7. Whole body autoradiograms obtained with pigmented rats demonstrated that specific binding of radioactivity to melanin containing tissues was noticed.

SORPTION OF PLUTONIUM‐237 BY TWO SPECIES OF MARINE PHYTOPLANKTON11

ABSTRACTThe adsorption of plutonium‐237, added from an acid solution, by two species of marine phytoplankton, Monochrysis lutheri Droop, a flagellated chrysomonad, and Phaeodactylum tricornutum Bohlin, a diatom, is governed by a passive mechanism. This is clearly indicated by the observation that the rapid rates of sorption were not significantly different for live and heat‐killed cells incubated at 24°C and 0°C. The Q10 values for the chrysomonad and the diatom of 0.95 and 1.18, respectively, are indicative of passive processes. The average ratio of (activity on algae/activity in filtrate) per unit volume at 24 h, the time when maximum levels of algal radioactivity were attained, of (32 ± 4) × 103 was not significantly different for the diatom or the chrysomonad. On a per cell basis, maximum levels of radioactivity were attained within 2 h. Less than 20% of the adsorbed 237Pu desorbed after 24 h.

Covalent binding of [ 14C]benzene to cellular organelles and bone marrow nucleic acids

Our objective was to determine whether reactive metabolites of benzene covalently bind to cellular proteins and nucleic acids of the hematopoietic organs and liver of the mouse. The distribution and binding of [ 14C]benzene after a single dose (880 mg/kg, s.c., 0.75 mCi/kg) were investigated at 3, 6, 12, and 24 hr. Maximum levels of radioactivity were found at 3 hr in liver, spleen, bone marrow, and blood. Maximum covalent binding occurred at 6 hr in liver, spleen, and bone marrow. Chemical fractionation of label derived from [ 14C]benzene indicated that 0.5, 7, and 17 per cent of the covalently bound label in liver, spleen, and bone marrow was recovered in the nucleic acids. Upon subcellular fractionation of liver, total radioactivity was localized chiefly in the cytosol (1723 dpm/mg protein) and mitochondria (1433 dpm/mg protein). Of the total radioactivity recovered in various organelles, mitochondria had the highest proportion covalently bound (25 per cent). These studies indicate that label derived from [ 14C]benzene covalently binds to nucleic acids of hematopoietic cells, the major site of toxicity. In addition, the high levels of covalent binding with macromolecules of the mitochondria suggest that their functions may be impaired by benzene.

Metabolic fate of T-2 toxin in a lactating cow

Excretion, transmission and metabolism of T-2 toxin, a trichothecene mycotoxin produced by Fusarium species, was studied in a lactating Jersey cow. After daily oral administration of unlabelled T-2 toxin by capsule for 3 consecutive days, tritium-labelled T-2 toxin was administered orally on day 4. Maximum levels of radioactivity in excreta and plasma were reached at the following times after dosing (with the concentration, expressed as T-2 toxin, in parenthesis): faeces at 44 hr (9·2 ppm), urine at 16 hr (5·5 ppm), milk at 16 hr (37 ppb) and plasma at 8 hr (64 ppb). By 72 hr almost all of the radioactivity had been eliminated in the urine and faeces, in a ratio of 3:7 respectively, and 0·2% of the dose given to the cow had been transmitted into the milk. Insignificant accumulation of the toxin in specific organs was observed. Chromatographic analyses of the tritium residues in cow tissues and excreta revealed that T-2 toxin was rapidly metabolized, yielding principally three major unknown metabolites (designated TC-1, TC-3 and TC-6) in addition to very polar metabolite(s) designated TC-8. Within the first 24 hr, the three major metabolites accounted for 30–40% of the extractable radioactivity in urine, 60–70% in milk and 50–60% in plasma. Minor amounts of unmetabolized T-2 toxin and of the metabolites HT-2 toxin, neosolaniol, and 4-deacetylneosolaniol were also detected in the cow.

Carbon-14 Distribution in Peanut Fruit Parts During Maturation Following 14CO Treatment of Intact Plants1

Abstract Effects of sampling date and developmental stage on the distribution of radioactivity within the crude ethanol, lipid, and starch fractions from fruit, seed coat, and seed of peanut were investigated. Major differences were found between the first and fourth feeding dates in the amount of 14C-labeled photo-synthate translocated to individual peanut fruit parts. Maximum levels of radioactivity in the pericarp, seed coat, and seed were attained at progressively later developmental stages as the respective part became the dominant metabolic sink. Within the fruit, maximum radioactivity in starch was reached during early maturity (stage 3) and total radioactivity generally decreased with successive feeding dates. Thus the level of photosynthate being translocated to a given fruit decreases as more fruit develop on the plant. Observed relationships between level of radioactivity and specific activity of fruit-part components were interpreted as indicating that metabolic reserves are built up in the fruit and seed coat during early maturation and utilized later during seed development and maturation when the level of available translocated photosynthate has diminished.

The study on metabolic fate of 5-fluorouracil-6-14C after percutaneous administration

The metabolic fate of 5-fluorouracil was studied in the rat by using 14C-labeled compound in ointment. Following the percutaneous administration of 5-fluorouracil in ointment, the rat excreted about 4% of the administered radioactivity in urine, 0.2% in feces, and 2.7% in respiratory CO2 within 72 hr, and about 90% of administered radioactivity remained at the site of application. Absorption of 5-fluorouracil in ointment from the skin was almost completed within the first 1 hr after ointment application and the maximum levels of radioactivity in rat tissues and blood also reached in about 1 hr after the application. Distribution of radioactivity in rat tissues was more highly located in the liver, kidneys, and in dermic and hypodermic tissues than in other tissues. After application of 0.5g per rat, of ointment containing radioactive 5-fluorouracil, the radioactive substances excreted in urine after 72 hr were unchanged 5-fluorouracil, α-fluoro-β-ureidopropionic acid, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine which were present in about 7.9%, 13.5%, 5.8%, 66.1%, and 3.7% of total radioactivity in the urine, respectively.

Distribution of tritium labelled delta 1-tetrahydrocannabinol in the rat brain following intraperitoneal administration.

Tritiated Delta(1)-tetrahydrocannabinol was injected intraperitoneally into rats and its distribution measured in the brain for up to 30 days after administration. The results showed that there was no selective distribution in any one area of the brain. The maximum levels of radioactivity occurred 1 h after the injection of the tetrahydrocannabinol, thereafter the levels fell very slowly, with demonstrable activity still present at the end of 30 days.