Biomedical subjects

J Edelson

Publications and source records attributed to J Edelson.

At least 73 records · Page 4Linked to original sources

PubMed1977

Absorption, distribution and metabolic fate of 2,3-dihydro-9H-isoxazolo-[3,2-b]quinazolin-9-one (W2429).

After oral administration to rats, mice, beagle dogs and human volunteers, 2,3-dihydro-9H-isoxazolo [3,2-b]-quinazolin-9-one (W 2429) is readily absorbed. The initial half-lives for the elimination from the circulation of these four species are about 240, 20, 40 and 120 min, respectively. Studies in the rat, using 9-14C-W-2429 and 3a-14C-W-2429, showed that more than half of the radioactivity is excreted in the urine. The major urinary metabolite in the rat and dog is a conjugated form of W-2429. Metabolic cleavage of the pyrimidone ring of W-2429 yields 3-(o-carboxyphenylimino)isoxazolidine, which in turn is converted to anthranilic and malonic acids. Anthranilic acid is acetylated and hydroxylated, and these products are excreted partly in the form of their glycine and glucuronic acid conjugates. The isoxazole ring of W-2429 is also dehydrogenated during metabolism to yield 9H-isoxanzolo-[3,2-b]quinazolin-9-one.

Administration, Oral↗

PubMed1977

Pharmacological properties of 2,3-dihydro-9H-isoxazolo[3,2-b]-quinazolin-9-one (W-2429. Part 2: General pharmacological investigation.

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Anesthetics, Local↗

PubMed1977

Species differences in the hepatic microsomal oxidation of nalidixic acid.

The kinetics of the conversion of nalidixic acid to the 7-hydroxymethyl derivative (M-HNA) by isolated liver microsomes of several common laboratory animal species was studied under optimal conditions. The order of activity was (from greatest activity to least): monkey greater than rabbit greater than mouse greater than rat greater than dog greater than cat. The formation of 7-HNA followed apparent Michaelis-Menton kinetics in all species except the cat; the substrate concentration at half-maximal velocity was highest with mouse microsomes, while the maximum velocity was greatest with monkey microsomes. Cat, dog, mouse and rabbit microsomes formed an additional metabolite, which was identified as 6-hydroxynalidixic acid, 1-ethyl-1,4-dihydro-6-hydroxy-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (6-HNA); in the cat, this was the major microsomal metabolite.

Animals↗

PubMed1977

Species differences in the metabolism of hycanthone.

The rate of excretion of labelled hycanthone has been determined in bile and urine from three strains of rats (Sprague-Dawley, hooded and Gunn), and from dogs, cats, rabbits and monkeys. Bile was the major route of excretion in all species; the half-life for excretion of total radioactivity ranged from 1.6 to 3.0 hours. Relatively little of the radioactivity was found in the urine, except in the monkey and notably in the cat. Most of the radioactivity in the bile and urine was found in conjugated form, or as polar metabolites; cat urine, however contained a high percentage of hycanthone and less polar metabolites. Some fifteen metabolites have been seen in bile, and/or urine, and nine from in vitro incubations with microsomal preparations. Five of these, including hycanthone, have been chemically characterized, and two others tentatively identified.

Animals↗

PubMed1977

A gas chromatography-mass fragmentographic method for the assay of ajmaline and its monochloroacetyl ester.

A gas chromatograph-mass fragmentography method for simultaneous assay of 17-monochloroacetyl-ajmaline (MCAA) and its hydrolysis product, ajmaline, is described. Recovery of both compounds from whole blood averaged 71%. About 5% of MCAA was hydrolyzed during the assay procedure. The method was accurate and precise to within a few percent. It was suitable for assays of blood levels in the dog after an i.v. dose of 2 mg/kg or an oral dose of 5 mg/kg.

Administration, Oral↗

PubMed1976

Interactions of chlorphenesin and divalent metal ions with phosphodiesterase.

Chlorphenesin inhibition of the hydrolysis of cyclic AMP by guinea-pig lung phosphodiesterase was reversed by the addition of exogenous magnesium ions. Chlorphenesin and theophylline inhibition of this enzyme was shown to be noncompetitive when the substrate concentration was low. Kinetic studies of the inhibition of beef heart phosphodiesterase by chlorphenesin and theophylline indicated that the substrate concentration was a factor in determining whether inhibition was competitive or noncompetitive. Calcium, cobalt and copper ions were inhibitory to guinea-pig lung phosphodiesterase. The inhibition due to chlorphenesin was partially reversed by low (40 mM or less) concentrations of barium ions; high concentrations of barium ions, or manganese ions, were inhibitory. The concentration of the divalent cation did not affect the type of inhibition that was observed.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1976

Hexachlorophene metabolism in rats: the hepatic route.

The terminal elimination rate of radioactivity from the bile of bile-duct cannulated rats, that had received hexachlorophene-14C via the hepatic portal vein, had an apparent first-order half-life of about 10 hr. Tissue distribution studies in these rats indicated that 35-47% of the carbon-14 of the dose was eliminated through the bile within 24 hr. Significant amounts of radioactivity were also found in the liver and carcass at that time; the brain was the only tissue that did not consistently have much higher concentrations of carbon-14 than the blood. The rate limiting step in the disposition of hexachlorophene may be excretion into the bile. A bile-feeding technique demonstrated enterohepatic circulation.

Animals↗

PubMed1975

Absorption, distribution, and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one in rats, dogs, and humans.

The absorption and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one (I) was studied in rats, dogs, and humans. Orally administered I was readily absorbed by all species. In the rat, orally administered I was converted to its metabolite, 5-chlorosalicylic acid, by the intestinal wall. The half-lives of blood radioactivity, after the oral administration of I-9-14C, were about 18 and 12 hr in the rat and beagle hound, respectively. In human subjects, no intact I was detected in the bloodstream; however, the clearance of the metabolite, 5-chlorosalicylic acid, had a half-life of about 33 hr. Cleavage of the oxazine ring of I generated 5-chlorosalicylic acid, which was excreted both in the free form and conjugated with glycine and glucuronic acid. The isoxazole moiety was converted to beta-hydroxybutyric acid and its metabolites carbon dioxide and fumaric, citric, alpha-ketoglutaric, succinic, and malic acids. Binding of I to plasma proteins was extensive but was less than that of 5-chlorosalicylic acid.

Animals↗

PubMed1974