Date of Award:

1982

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

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Department name when degree awarded

Toxicology

Advisor/Chair:

Joseph C. Street

Abstract

Selected drugs are being utilized as models of putative colon carcinogens in a study of the influence of major types of dietary fiber upon drug pharmacokinetics. Adult, male Wistar rats were pretreated with standardized, isocaloric hydrated gelatin diets containing no fiber or 15% (w/w) cellulose, lignin, hemicellulose (metamucil), or pectin for 30 days. An additional group was fed lab chow ad libitum as a reference control.

The pharmacokinetics of acetaminophen, FD & C Red No. 2 and mirex were examined following oral administration in three separate experiments. Among fiber types, pectin and hemicellulose (Metamucil) caused higher peak plasma concentrations of acetaminophen and faster rates of absorption. There was no effect of fiber type on the rate of acetaminophen elimination as determined by the interpretation of the plasma data using the computer programs AUTOAN2 and NONLIN69. Minimal quantities of Red No. 2 were absorbed from the rat intestinal tract, but its microbial metabolite, naphtionic acid, was readily taken up. Pectin produced a 5-fold higher peak plasma concentration of naphthionic acid than control animals on fiber free diet. Cellulose feeding lowered peak plasma concentration of naphthionic acid compared to the fiber control animals. Lack of any fiber in the diet produced a prolonged peak plasma concentration of napthionic acid. The metabolism of Red No. 2 to naphtionic acid by rat cecal contents was augmented by pectin feeding, alone among fiber types. Red No. 2 decreased intestinal transit times in all diet groups, including controls, with there being no difference in transit times between fiber-fed and control animals. Hemicellulose and pectin feeding lowered peak plasma concentrations of mirex compared to control and cellulose fed animals. Lignin, however produced higher peak plasma concentrations of mirex and a 4-fold higher rate of mirex elimination when compared to the fiber-free control group.

These differential effects of specific fiber types upon the absorption and disposition of acetaminophen, Red No. 2 and mirex were not consistantly related to the chemical binding-capacities of the fibers of their water-holding capacities.

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Included in

Toxicology Commons

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