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J W Barnhart

Publications and source records attributed to J W Barnhart.

12 recordsLinked to original sources
PubMed1988

Probucol enhances cholesterol transport in cultured rat hepatocytes.

Probucol has been investigated extensively in vivo and ex vivo. However, little information is available on direct treatment of cultured cells. Treatment of cultured hepatocytes by 1 to 10 microM probucol for 16 to 20 hours had no apparent deleterious effect on the cell, and in fact decreased lactic dehydrogenase leakage. Also, total cellular cholesterol was increased, cholesterol synthesis was decreased, and cholesterol esterification was increased. The increase in cellular cholesterol was not the result of increased lipoprotein uptake but appeared to be the result of an interaction between cell and lipoprotein in which the cell became enriched and the lipoprotein depleted in cholesterol. This type of change in lipoprotein composition after treatment is also observed clinically.

Animals↗
PubMed1977

Gas chromatographic determination of hydrocodone in serum.

A procedure for the determination of hydrocodone (dihydrocodeinone) in serum has been developed. Hydrocodone and N-isobutyldihydronorcodeinone, the internal standard, are extracted from serum by chloroform-isopropyl alcohol (9:1, v/v). The extracts are purified by back-extraction into 0.1 N sulfuric acid and a final basic extraction into benzene. The pentafluorophenylhydrazone derivatives are formed and determined using electron capture gas chromatography. As little as 1 ng/ml of hydrocodone in serum can be determined. A closely related compound and potential metabolite, dihydronorcodeinone, does not interfere. Serum hydrocodone levels were determined in dogs after oral and intravenous doses of 0.5 mg/kg, and in humans after a 10-mg oral dose of the bitartrate. A mean peak serum drug concentration of 23.6 ng/ml and a terminal half-life of 3.8 h resulted from the human study. The terminal half-life in serum was 1.8 h after the intravenous dose in dogs.

Administration, Oral↗
PubMed1977

An overview of the biochemical pharmacology of probucol.

Probucol was effective in lowering serum total cholesterol in mice at dietary livels as low as 0.0075%. It was also effective after a single 100 mg/kg I.V. dose in mice. The incorporation of acetate-(14)C into liver lipids of rats and mice was not significantly affected by probucol, although the results, especially in mice, make it impossible to rule out such an effect. Cholesterol absorption was estimated in rats using a dual isotope technique. The observed reductions were not statistically significant. Several liver enzyme activities were determined after probucol treatment in rats, and a significant elevation (32%) was observed in only one, glutamic dehydrogenase. Serum cholesterol was lowered markedly in cholesterol-fed cynomolgus monkeys by probucol. There was no effect on the excretion of neutral steroids and the observed increase in fecal bile acids after drug treatment could not be confirmed statistically.

Animals↗
PubMed1977

Hypolipidemic arylthioalkanoic acids.

A series of arylthioalkanoic acids related to probucol was studied for hypolipidemic activity. Homologation of the alkyl side chain led to marked changes in the serum cholesterol and serum triglyceride lowering activity in rats with the best combination of properties appearing in compound 7, 2-[3,5-di-tert-butyl-4-hydroxyphenyl)thio]hexanoic acid. Modification of the ring substitution failed to improve the activity despite the empirical observation that lipophilic substitution was necessary. Removal of the phenolic hydroxyl produced compound 23 with properties similar to 7 but of somewhat lower activity. Replacement of the sulfur by oxygen increased the toxicity of the series. Resolution of racemic 7 did not change the activity of the compound. The LD50 in mice of 7 was between 5000 and 10 000 mg/kg and compound 7 has been submitted for human clinical evaluation.

Animals↗