1. A single oral dose of [(14)C]Ionox 100 to rats is almost entirely eliminated in 11 days: 89.1-107.2% of the (14)C is excreted and 0.29+/-0.02% of the dose is present in the carcass plus viscera after removal of the gut. Rats exhibit an individual variation in the elimination pattern, 15.6-70.8% of (14)C being excreted in the urine and 75.2-27.0% in the faeces during 11 days. 2. After the oral administration of [(14)C]Ionox 100 to dogs, 87.1-90.3% of the (14)C is excreted in the faeces and urine during 4 days. 3. Dogs and rats do not show a species difference in this pattern of elimination. 4. The rate of elimination from dogs and rats given a single dose of Ionox 100 is not affected by the size of the dose and the presence of triglyceride fat in the diet. 5. Ionox 100 is completely metabolized in dogs and rats: unchanged Ionox 100 is absent from the urine and faeces, and from the carcass when elimination is complete. In rats, 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 50-85% of a dose of Ionox 100 and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 47-10%; in dogs, the unconjugated acid accounts for 85% and the ester glucuronide for 10-12%. 3,5-Di-tert.-butyl-4-hydroxyhippuric acid is not formed. Other metabolites, which have been detected in small quantity in the faeces and urine of animals dosed with Ionox 100, have not been identified. 6. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid and (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid are also the major metabolites of Ionol (2,6-di-tert.-butyl-p-cresol) in rats. 7. The elimination of Ionox 100 metabolites from rats is faster than that of Ionol and its metabolites. Unlike Ionol, unchanged Ionox 100 could not be detected in the bodies of these animals.
1. A large proportion of a single oral dose of [(14)C]Ionox 220 to rats is eliminated in 24 days: 89.3-97.4% of the label is excreted in the faeces (much of this is eliminated in the first 4 days after dosage), 1% in the urine and less than 0.1% in the expired gases; 4.06% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 2. About 87% of (14)C in the faeces is due to unchanged antioxidant, 5% to the quinone methide, 5% to the free acid and 3% to an unidentified polar constituent. Three-fifths of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid and the remainder to the ester glucuronide. In three individual animals, one-half of (14)C in the bile is due to the free acid, one-quarter to the ester glucuronide and the remainder to unchanged antioxidant, whereas in another all of (14)C in the bile is due to Ionox 220. About 97% of (14)C in the body fat is due to unchanged antioxidant and the remainder to the free acid. 3. Up to 20% of a single oral dose of Ionox 220 is absorbed in rats: 13-14% is metabolized. 3,5-Di-tert.-butyl-4-hydroxybenzoic acid accounts for just over 5% of a dose of Ionox 220, 3,5-di-tert.-butyl-4-hydroxybenzoyl-beta-d-glucopyranosiduronic acid for less than 0.4%, the quinone methide for just over 5% and an unidentified compound for less than 3%. 4. The physiological and biochemical implications of ingesting Ionox 220 are discussed.
By examining the effects of commercially available preparations of glucose oxidase on chromatographically pure maltose, maltotriose and maltotetraose, it has been shown that both the "crude" and "pure" preparations cannot be regarded as specific for glucose.
1. Unchanged Ionox 330 is quantitatively eliminated in the faeces of dogs, rats and man after oral administration, and (14)C is absent from the urine and expired gases of rats intubated with [(14)C]Ionox 330. Dogs and rats do not show a sex difference in this pattern of elimination. 2. Quantitative elimination of [(14)C]Ionox 330 and the absence of (14)C in the carcass and viscera of rats 72hr. after dosage show that this substance does not accumulate in the body. 3. No metabolites are formed in consequence of the ingestion of Ionox 330. 4. Rats eliminate three-quarters or more of a dose (285.7mg./kg. body wt.) of Ionox 330 in 24hr. and the remainder during 24-48hr., and dogs eliminate the whole dose (90mg./kg. body wt.) within 48hr. and a variable proportion within 24hr. These rates of elimination are consistent with the passage of unabsorbed material through the alimentary canal. 5. After removal of the alimentary canal, radioactivity is absent from the carcass and remaining viscera of rats 8, 16 and 24hr. after ingestion of [(14)C]Ionox 330, and this strongly suggests the absence of alimentary absorption. 6. The absence of (14)C in the 24hr. bile of animals with biliary fistulae establishes that [(14)C]Ionox 330 is not absorbed from the gastro-intestinal tract.
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