Search

Methylglucamine is a commonly used cation in radiocontrast media. The present study sheds light on its fate in the rat. When administered intraperitoneally, 93% of the compound was excreted unchanged in the urine in 24 hr. When administered orally, about 15% of the dose was found in the urine, about 40% in the faeces and 20% in expired air in 24 hr. When administered orally to rats whose gut flora had been depleted by treatment with neomycin sulphate, 19% was excreted in the urine, 69% in the faeces and 3% in expired air in 72 hr. This indicated that the gut flora played a role in the degradation of the compound and its eventual loss as expired carbon dioxide.

The metabolism and excretion of the fat-soluble bisazo dyes Sudan III and Sudan IV have been studied in the rat. Limited absorption of Sudan III from the gastro-intestinal tract after oral dosage, slow back diffusion of both dyes across the intestinal wall after intraperitoneal injection and absence of either dye in urine or bile after intraperitoneal (Sudans III and IV) or oral (Sudan III) administration have been demonstrated. Studies with [ 3 H]Sudan III showed that this dye is probably cleaved and hydroxylated in the body to yield p -aminophenol after parenteral dosage. Inconsistencies between these results and those of earlier workers are discussed in relation to the composition of the pure and commercial dyes used.

The metabolism of diphenylamine has been studied in the rat, rabbit and man. The major metabolites in these species were 4-hydroxydiphenylamine and 4,4′-dihydroxydiphenylamine. The rabbit in addition excreted small amounts of 2-hydroxydiphenylamine and unchanged amine. The O-sulphate and O-glucuronide (as the tri-O-acetylmethyl ester) conjugates of 4-hydroxydiphenylamine were isolated from rabbit urine. Quantitative studies in rats showed that [14C]-diphenylamine is excreted in both urine and bile and is rapidly eliminated from the body.

Single oral doses of tartrazine and 1-(4-sulphophenyl)-3-methyl-4-(4-sulphophenylazo)-5-pyrazolone(SMSP), each labelled with 'SS in the 1-(4-sulphophenyl) group, were largely excreted in the faeces of rats. Small amounts of radioactivity excreted in the urine of animals given either compound were found to be sulphanilic acid and 4-sulphophenylhydrazine. 4-[ 35 S]Sulphophenylhydrazine was also metabolized to sulphanilic acid after oral dosage but was metabolized much less readily after intravenous dosage. SMSP, labelled with 3- 14 C, showed an excretion pattern similar to that of the 3 IS-labelled material but some 14 CO 2 was exhaled. The metabolism of these compounds after oral dosage appears to be mediated by the gut flora.

Anaerobic incubation of 1-(4[ 35 S]sulphophenyl)-3-methyl-4-(4-sulphophenylazo)-5-pyrazolonewith Proteus vulgaris or rat-gut contents produces labelled sulphanilic acid and 4-sulphophenylhydrazine. Similar incubation with 4[ 35 S]sulphophenylhydrazine gave little conversion to sulphanilic acid with Proteus but good conversion with gut contents. The results obtained support the view that intestinal microflora are mainly responsible for the metabolism of water-soluble pyrazolone dyes in rats.

The metabolism and excretion of three aryldihydro-striazines were studied using rats. The compounds investigated were 4,6-diarnino-l,2-dihydro-2,2-dimethy-lp-hle nyl-s-triazine (I),t he prototype of the series; 4,6-diamino-1-(3,4-dichlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine (11); and N-( m -tolyl)- p -(4,6-diamino-l,2-dihydro-2,2-dimethyl- s -triazin-1-yl)hydrocinnamide (III). All three compounds were excreted rapidly. Urinary excretion was favored by a lower molecular weight, and biliary excretion was favored by a higher molecular weight. The overall elimination rates of I and III were similar, I being excreted predominantly in urine and III (considerably metabolized) in bile. The overall elimination rate of II, excreted mainly in urine, was lower than for the other two triazines. A large percentage (and probably all) of the dose of I and 11 was unmetabolized. Metabolism of III does not appear to involve the phenyldihydrotriazine moiety. This broad view of the metabolism and excretion of the three triazines gives no particular insight into why II, although a more potent inhibitor of dihydrofolate reductase and of L-1210 tumor cell cultures, has been found to compare very poorly with III in its in uiuo antineoplastic activity in rats.

The urinary and biliary metabolites of 1-phenyl-3-carboxy-4-phenylazo-5-pyrazolone (PCPP) and 1-phenyl-3-methyl-4-phenylazo-5-pyrazolone (PMPP) have been identified. PCPP is excreted partly unchanged and partly as the 4-hydroxyphenylazo derivative. PMPP is also excreted as these compounds and so is 1-phenyl-3-hydroxymethyl-4-phenylazo-5-pyrazolone. The oxidation of the methyl group of PMPP appears to take place before hydroxylation of the 4-phenylazo ring. This hydroxylation seems to be specific since no oxidative attack was found to occur in the 1-phenyl ring. Using 14 C-labelled PCPP quantitative data for the excretion of this compound and its metabolites are reported. No reduction of this compound results from intraperitoneal injection.

The metabolism of 4-nitroaniline, 2,6-dichloro, 2,6-dibromo- and 2,6-dimethyl-4-nitroaniline has been studied in rats. 4-Nitroaniline is excreted partly unchanged and also as 4-phenylenediamine and 2-amino-5-nitrophenol. Both halogenated derivatives undergo replacement of the nitro group by hydroxyl to yield halogenated 4-aminophenols. The chloro compound gave some of the corresponding phenylenediamine. Metabolites from the methylated derivative were unidentified but no aminophenols or phenylenediamine derivatives were detected. The results have been quantitated using isotopically-labelled compounds, all of which were well absorbed and rapidly excreted. The mechanism of the metabolic replacement of the nitro group by hydroxyl is discussed.

The excretion and metabolism of tartrazine has been studied in the rat, rabbit and man. The nature of the excretory products depends upon the route of administration. Intraperitoneal injection leads to the excretion of unchanged colouring. Oral dosage results in the excretion of equivalent amounts of sulphanilic acid which is partly conjugated. A quantitative excretion study has been carried out. The reasons for the resistance of tartrazine to the action of mammalian azo reductase are discussed.