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T L Williams

Publications and source records attributed to T L Williams.

63 records · Page 4Linked to original sources

Insulin secretion from pancreatic islets: effect of growth hormone and related proteins.

Insulin responses to clinical grade human growth hormone (hGH), intact hGH, naturally occurring diabetogenic substance (NDS), and subtilisin cleaved forms of hGH (S1 and S3) were studied using hypophysectomized rat pancreatic islets. While clinical grade hGH (200 microgram/ml) elicited a prompt and sustained release of insulin, purified intact hGH (200 microgram/ml) did not. Naturally occurring diabetogenic substance, isolated from clinical grade hGH preparations, stimulated insulin release at 200 ng/ml. Upon repeat stimulation with NDS, a significantly greater insulin release than with initial stimulation was observed. Although S3 (200 microgram/ml) elicited significant insulin release, S1 (200 microgram/ml) did not. Direct stimulation of insulin release with clinical grade hGH is not due to intact hGH but another proteins(s) such as NDS. Enzymic modification of intact hGH appears to enhance insulin stimulatory capacity.

Animals↗

Disposition of dobutamine in the dog.

The disposition of dobutamine, a potent inotropic catecholamine, has been examined in the dog. A sensitive assay has been developed for dobutamine allowing the measurement of the drug at plasma concentrations as low as 1 ng/ml. The short plasma half-life of dobutamine from the plasma to the tissue. When 14C-dobutamine was administered, the plasma half-life of radioactivity was 1.9 hours. The circulating radioactivity consists mainly of the glucuronide conjugate of 3-O-methyldobutamine. During continuous intravenous administration of dobutamine, plasma levels of metabolites reached a maximum between 3 and 4 hours. During a 48-hour time period after administration of 14C-dobutamine, 67% of the radiolable was excreted in the urine and 20% in the feces. In dogs having cannulated bile ducts, 30 to 35% of the administered drug was excreted in the bile. The major urinary metabolites were the glucuronide conjugates of dobutamine and 3-O-methyldobutamine.

Animals↗

Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat.

The absorption, excretion, and metabolism of propionyl erythromycin (PE) has been studied in the rat. The major routes of metabolism of PE are ester hydrolysis and N-demethylation. The rates of these two reactions have been examined in vivo using radiolabeled PE. The plasma half-life of the ester is 5.5 hr. The correlation of blood levels of radioactivity with 14CO2 production indicates that the ester is continually hydrolyzed after absorption. The half-life of the dimethyl-amino moiety of the desosamine sugar is estimated at 1.5 hr. This relatively short half-life compared to that of the ester is supported by the fact that at 3.5 hr after dosing there is twice as much desmethyl-PE in plasma as PE. After oral administration of either 14C-PE or 14C-erythromycin, 70% of the radioactivity is absorbed in 6 hr. The major route of excretion is via bile. Approximatley 40% of the absorbed dose is excreted in bile in the first 6 hr after dosing. Tissue levels of radioactivity after administration of 14C-erythromycin or 14C-PE indicate that PE or a metabolite accumulates in the tissue during chronic dosing, whereas erythromycin-related levels are similar after single or multiple doses.

Animals↗

Metabolism of propionyl erythromycin lauryl sulfate. II. Fate of the lauryl sulfate moiety in the rat and man.

The absorption, excretion, and metabolism of [1-14C]lauryl sulfate as either the sodium or propionyl erythromycin salt has been studied in the rat and man. In the rat 88% of the radiolabel from propionyl erythromycin [1-14C]lauryl sulfate was excreted in the urine in the 24-hr period following a single oral dose. More than 95% of the radiolabel was excreted as the metabolite butyric acid 4-sulfate. This metabolite was shown to be derived from carbons 1-4 of the lauryl sulfate moiety. There was no evidence of sulfate cleavage in the rat. In man 51-59% of the administered ratioactivity was recovered in the urine. The major excretion product was butyric acid 4-sulfate accounting for approximately 95% of urinary radioactivity. The remainder was unchanged lauryl sulfate. A significant portion of the radiolabeled propionyl erythromycin lauryl sulfate was converted to 14CO2 indicating that the sulfate linkage was cleaved. A minimum value of 9-16% of the dose was metabolized in this manner.

Animals↗