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Biomedical subjects

R T Williams

Publications and source records attributed to R T Williams.

At least 73 records · Page 4Linked to original sources
PubMed1978

The fate of saccharin impurities: the excretion and metabolism of [3-14C]Benz[d]-isothiazoline-1,1-dioxide (BIT) in man and rat.

1. The 14C label of [3-14C]benz[d]isothiazoline-1,1-dioxide (BIT) (40 mg/kg) was rapidly eliminated (97% dose in 24 h), largely in the urine (92% dose in 24 h), after oral administration to rats. Larger doses (400 mg/kg) were eliminated more slowly after oral or parenteral administration (45--60% within 24 h) mostly in the urine (42--53%). Little 14C (2--3% dose) was present in the faeces after intraperitoneal (400 mg/kg) or low oral (40 mg/kg) doses, but the presence of larger amounts (12% dose) after larger oral doses (400 mg/kg) indicated incomplete absorption. 2. Metabolites identified in the urine of rats were saccharin (about 30% of urinary 14C), 2-sulphamoylbenzoic acid (about 35% urinary 14C) and 2-sulphamoylbenzyl alcohol (15% urinary 14C) in addition to unchanged compound (5--10% urinary 14C). The urine also contained a polar, labile metabolite that gave BIT on acid hydrolysis. The pattern of metabolism was not significantly affected by dose or route of administration. 3. In man, urine was the major route of elimination of 14C (93% dose) after administration of 14C-BIT (0.5 mg/kg). Negligible 14C was recovered in the faeces (less than 1% dose). Excretion was rapid (59% dose in 6 h; 80% dose in 12 h) and little 14C was eliminated on the second (3%) or subsequent days after dosing. 4. Identified metabolites in man included saccharin (about 50% of urinary 14C), 2-sulphamoylbenzoic acid (7% urinary 14C) and 2-sulphamoylbenzyl alcohol (8% urinary 14C unconjugated and 40% conjugated) with negligible unchanged compound. Only traces of the polar labile metabolite were detected. 5. the possible significance of metabolic interrelationships of toluene-2-sulphonamide and BIT to studies on the metabolism of saccharin are discussed.

Animals↗
PubMed1978

The fate of saccharin impurities. The excretion and metabolism of [14C]toluene-4-sulphonamide and 4-sulphamoyl[14C]benzoic acid in the rat.

1. 4-Sulphamoyl[carboxy-14C]benzoic acid was rapidly eliminateda after oral administration to rats (94% dose in 24 h). After 6 days most of the 14C (73-83% dose) was recovered in the urine with significant amounts (18-32% dose) in the faeces due to incomplete absorption. 2. The 14C in the urine and faeces was unchanged 4-sulphamoylbenzoic acid. No 14CO2 was detected in the expired air. 3. After oral administration of [methyl-14C]toluene-4-sulphonamide to rats the label was rapidly eliminated largely in the urine (66-89% dose) with little in the faeces (2-8% dose). The 14C in the faeces was 4-sulphamoylbenzoic acid, which probably originated in the tissues since the gut flora was unable to effect this biotransformation. 4. The urine of rats given [14C]toluene-4-sulphonamide contained 4-sulphamoylbenzoic acid as the major metabolite (93% of the urinary 14C) together with small amounts of unchanged compound (1.5-2.3% of urinary 14C), 4-sulphamoylbenzyl alcohol (2.0-3.9%), 4-sulphamoylbenzaldehyde (0-1.5%) and at higher doses N-acetyltoluene-4-sulphonamide (2.1-2.3%).

Animals↗
PubMed1977

Comparative metabolism of the amphetamine drugs of dependence in man and monkeys.

The use of animal models to study drug dependence and tolerance requires that the species used metabolizes the drugs like man, a condition frequently not fulfilled by non-primate species. The metabolic fate of several amphetamine drugs, namely amphetamine, norephedrine, chlorphentermine and phenmetrazine, in the rhesus monkey and the tamarin and two non-primate species has been investigated and compared to that found for man. The findings show that the two primate species metabolize these drugs in a manner similar to that in man.

Amphetamines↗
PubMed1977

Effect of p-nitro-substitution on the metabolism of benzoic acid in the Indian fruit bat.

The introduction of a nitro-group at the 4-position of benzoic acid does not alter remarkably the metabolic pattern of benzoic acids in the fruit bat. It is shown here that the Indian fruit bat does not form hippuric acid with nitro benzoic acid, the main conjugate being the glucuronide in addition to other conjugates suspected to be p-amino benzoylglutamic acid and p-nitro benzoylglutamic acid respectively. More unmetabolized nitrobenzoic acid is present in the 24hr. urine than reported for unsubstituted benzoic acid. The Indian fruit bat exhibits an appreciable ability to reduce the nitrogroup in nitrobenzoic acid to the amino compound and to acetylate the amino group to the acetamido compound.

Animals↗
PubMed1976

Tolerance to amphetamine in two species (rat and guinea pig) that metabolize it differently.

It has been proposed that p-hydroxynorephedrine, a metabolite of amphetamine, is responsible for the tolerance that occurs to this drug. To test this idea, the development of tolerance to amphetamine has been examined in two species, the rat and the guinea pig, the former of which produces p-hydroxynorephedrine from amphetamine while the latter does not. In both species, tolerance develops to the anorectic and hyperthermic actions of amphetamine, and similar changes in the pattern of behavioural stimulation are seen.

Animals↗
PubMed1976

Urinary metabolites of p-hydroxyamphetamine in man, rat and guinea-pig.

1. The metabolism of (+/-)-p-hydroxy[14C]amphetamine has been studied in the rat, guinea-pig and man. 2. Most of the administered 14C was excreted in the urine within the first 24 h (64-92%), and was present mainly as free and conjugated p-hydroxy[14C]-amphetamine. In the female rat and female guinea-pig the conjugate was a glucuronide, but in man, who received a much smaller dose, the conjugate was a sulphate ester. A sex difference in conjugation was found in the rat, the female partly conjugating the drug but not the male. 3. Small quantities (1-6% of dose) of p-hydroxynorephedrine, a putative false neurotransmitter, were found in the urine of the three species. 4. Some oxidative degradation of the side chain of p-hydroxyamphetamine occurred in rat and guinea-pig since small amounts of p-hydroxybenzoic acid (1-3%) were detected in the urine.

Amphetamines↗
PubMed1975

The metabolism of (-)-ephedrine in man.

The metabolic fate of orally administered (-)-[14C]-ephedrine has been studied in 3 human subjects and the urinary excretion of metabolites determined quantitatively by solvent extraction, paper chromatography and reverse isotope dilution procedures. Following an oral dose of the drug (0.35 mg/kg, 1.6 muCi), 97% of the dose was excreted in the urine within 48 h, 88% in the first 24 h. Unchanged drug was the major urinary excretory product (53-74%), with N-demethylation occurring to a variable extent (8-20%) although there was little interindividual variation in urine pH. Oxidative deamination was also variable (4-13%); the main identified products of this were benzoic acid (free and conjugated) and 1,2-dihydroxy-1-phenylpropane (free and conjugated). No phenolic metabolites could be detected, and thus it would appear that these compounds cannot be implicated in the acquisition of tolerance to ephedrine which can occur on repeated dosage.

Adult↗