The gastrointestinal absorption,tissue distribution,urinary excretion and metabolism of N-(2-aminoethyl)-glycine (AEG) in the rat

Radiolabeled N-(2-aminoethyl)-glycine (AEG) was synthesized and various aspects of its bioavailability were evaluated. AEG was rapidly and completely taken up by the small intestine of the rat. It was quickly absorbed into the portal vein. Most of the absorption took place during the first hour, with a peak at 30 min. Entry of this compound into the intestinal mucosal cell may be by a mechanism not involving active transport. Of many organs examined, only the liver took up significant amounts of AEG. The latter neither crossed the brain barrier nor was metabolized. Total urinary excretion (as intact AEG) averaged 80% of the administered dose within 4 hours and nearly 100% by 10 hours. Excluding the neutral-acidic amino acids and ammonia, AEG represented >99% of the ninhydrin positivity in the urine. AEG is thus an example of a substance which is rapidly and totally absorbed, as well as quickly and completely excreted.     

Copper absorption,endogenous excretion,and distribution in Sprague-Dawley and lean (Fa/Fa) Zucker rats

We previously observed a rapid reduction in plasma ceruloplasmin activity in lean Zucker (Fa/Fa) rats fed a marginal copper (Cu)-deficient diet compared to similarly fed obese Zucker (fa/fa) and lean Sprague-Dawley rats. In an effort to understand the mechanisms underlying this response, we utilized the isotope dilution method to investigate the absorption and excretion of Cu in lean Zucker rats fed control and marginal Cu diets. Sprague-Dawley (SD) and homozygous lean Zucker rats were fed either a Cu-adequate (Cont; 7.5 μg Cu/g diet) or a low Cu (Low; 1.1 μg Cu/g diet) casein-based diet for 23 d. Two weeks following initiation of the dietary treatment, each rat was injected intramuscularly (im) with 11.2 μCi of⁶⁷Cu. Urine and feces were collected daily. On the 9th d following isotope injection, rats were killed and tissues collected. Significant dietary effects were observed in the relative absorption and endogenous fecal excretion of⁶⁷Cu. The tissue distributions of nonisotopic Cu and⁶⁷Cu activity were also different between dietary treatments. Tissues from rats fed the low-Cu diet typically had high concentrations of⁶⁷Cu and low concentrations of nonisotopic Cu compared to controls. An increase in relative⁶⁷Cu absorption was evident for rats fed the low-Cu diet (57.2 and 39.3%, for SD Low, Zucker Low, respectively, and 17.9, and 28.5% SD Cont and Zucker Cont, respectively). Rats fed the low-Cu diet also had reductions in endogenous fecal excretion of⁶⁷Cu compared to their respective controls. Although strain effects were not evident for either percent Cu absorption or endogenous fecal Cu excretion, the relative adaptive changes appeared more marked for the Sprague-Dawley rats compared to the lean Zucker rats.     

(14C)Ethylenethiourea: distribution, excretion, and metabolism in pregnant rats.

Following administration of single oral doses of [14C]ethylenethiourea (ETU) to pregnant rats maternal blood maintained peak radioactivity for 2 h, and the radioactivity was dispersed uniformly between the red blood cells and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. Twenty-four hours after treatment all tissues examined, except blood, were relatively clear of radioactivity and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites from Sephadex separation suggested that ethylenethiourea was degraded very little. The teratological mechanism is discussed.     

Pharmacokinetic, tissue distribution and excretion of ginsenoside-Rd in rodents

Ginsenoside-Rd (GS-Rd) is one of the major active components of Panax ginseng, and was shown to have the protective effects against several insults. However, we still lack some basic knowledge of GS-Rd, including its pharmacokinetic, tissue distribution and excretion in vivo in experimental animal, such as mice and rats. In this study, HPLC and radioactive tracer assays were performed to determine pharmacokinetic, tissue distribution and excretion of GS-Rd in rodents. After intravascular administration with 20, 50 or 150 mg/kg GS-Rd, the dynamic changes of GS-Rd concentrations in plasma were consistent with a two-compartment model while the concentration of 3H-labeled GS-Rd was rapidly reached the peak in plasma, and distributed to various tissues, among which the highest concentration was observed in the lung.     

Toxicity of tobramycin in single and multiple administrations to laboratory animals]

The LD50 of tobramycin sulphate administered intravenously, intraperitoneally, subcutaneously and orally to albino mice was 77 (73--82), 262 (234--294), 560 (500--627) and greater than 10500 mg/kg respectively. With an increase in the rate of intravenous administration tobramycin toxicity increased. When tobramycin sulphate was administered subcutaneously daily in multiple doses equivalent to the daily therapeutic doses from humans (calculated for the body surface) and in the doses 2--3 times higher than the above therapeutic ones, the function of the kidneys, liver and the Preier's reflex did not significantly change. When the doses were 8--10 times higher than the therapeutic ones, an increase in the urea level in the blood serum, disappearance and a decrease in the Preier's reflex were observed. The impairment of the kidney function was accompanied by degenerative changes in the convoluted tubules of the kidneys, ischemia of the renal glomeruli and appearance of protein secretion in their capsule cavities. The picture of the peripheral blood did not suffer significant changes. The studies on the acute and chronic toxicity of tobramycin sulphate prepared at the Institute of New Antibiotics showed that the drug did not differ from the import tobramycin samples.     

Intestinal absorption and tissue distribution of [14C]pyrroloquinoline quinone in mice.

Pyrroloquinoline quinone (PQQ) functions as a cofactor for prokaryotic oxidoreductases, such as methanol dehydrogenase and membrane-bound glucose dehydrogenase. In animals fed chemically defined diets, PQQ improves reproductive outcome and neonatal growth. Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion. About 28 micrograms of PQQ (0.42 microCi/mumol), labeled with 14C derived from L-tyrosine, was administered orally to Swiss-Webster mice (18-20 g) to estimate absorption. PQQ was readily absorbed (62%, range 19-89%) in the lower intestine, and was excreted by the kidneys (81% of the absorbed dose) within 24 hr. The only tissues that retained significant amounts of [14C]PQQ at 24 hr were skin and kidney. For kidney, it was assumed that retention of [14C]PQQ represented primarily PQQ destined for excretion. For skin, the concentration of [14C]PQQ increased from 0.3% of the absorbed dose at 6 hr to 1.3% at 24 hr. Furthermore, most of the [14C]PQQ in blood (greater than 95%) was associated with the blood cell fraction, rather than plasma.     

Absorption, tissue distribution, metabolism and excretion of ormetoprim and sulphadimethoxine in cod (Gadus morhua) after oral administration of Romet30

Uptake, tissue distribution, metabolism and elimination of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined in Atlantic cod (Gadus morhua) following oral administration of Romet³⁰ at a dose of 5 mg OMP and 25 mg SDM per kilogram fish. Absorption and elimination was rapid for OMP and slow for SDM characterized by peak plasma concentrations (C_max) of 1.44 and 20.93 μg ml^?1 after 7 and 59 h, respectively, and plasma elimination halflives (t_1/2β) of 7 h for OMP and 56 h for SDM. High concentrations of SDM were found in the bile indicating high biliary excretion of this drug whereas moderate concentrations of N‐acetylated SDM were found in tissues and bile indicating N‐acetylation to be a less important metabolic pathway for SDM in cod. The biliary concentration of OMP was low.     

Toxicity, pharmacokinetics and pharmacodynamics of the Soviet bleomycin, bleomycetin, in a single administration to laboratory animals]

Toxicity of bleomycetin (bleomycin A2) administered intravenously, intraperitoneally, subcutaneously or intramusculary in a single dose to animals was almost identical. On its oral administration bleomycetin was 10--14 times less toxic than on its parenteral use. Rats were somewhat less sensitive to bleomycetin than mice. Bleomycetin had no significant effect on the level of the arterial pressure, respiration, ECG characteristics and elements of the vegetative nervous system in narcotized cats. After a single intravenous or subcutaneous administration to rabbits bleomycetin was detectable in the blood for 4--5 hours. The highest bleomycetin levels were registered in the skin, kidneys and lungs. Bleomycetin was mainly excreted with the urine.