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Biomedical subjects

S C Mitchell

Publications and source records attributed to S C Mitchell.

At least 109 records · Page 6Linked to original sources
PubMed1986

Sulphoxidation of S-carboxymethyl-L-cysteine in the rhesus monkey (Macaca mulatta), cynomologus monkey (Macaca fascicularis), African green monkey (Cercopithecus aethiops) and the marmoset (Callithrix jacchus).

The metabolic pathways giving rise to the urinary metabolites of S-carboxymethyl-L-cysteine have been identified for the rhesus, cynomologus, African green and marmoset species of monkey. The formation of a sulphoxide metabolite from the sulphide precursor is a reaction important in these species. The metabolic profile displayed by the marmoset was distinct from the three Old World species, with the rhesus and cynomologus being similar to man.

Animals↗
PubMed1985

Lack of congruence of S-carboxymethyl-L-cysteine sulphoxidation and debrisoquine 4-hydroxylation in a Caucasian population.

One-hundred-and-twenty volunteers and three families were investigated for possible association between the sulphoxidation of S-carboxymethyl-L-cysteine and the debrisoquine hydroxylation polymorphism. The observed individual variations in these two metabolic reactions were shown not to be concordant (rs = 0.068) and any heritable factors controlling the major aspects of these phenomena do not co-segregate.

Adolescent↗
PubMed1985

The metabolism of phenothiazine in the neonatal calf: identification of drug-polypeptide conjugates from urine.

The presence of a polypeptide conjugate fraction in the urine of young calves after oral dosing with phenothiazine has been confirmed. Four different polypeptide conjugates, containing up to six amino acids attached to phenothiazine or leucophenothiazone via the carboxyl terminal of the chain, have been isolated, characterized and sequenced. In addition, several minor polypeptide conjugates have been observed. The literature pertaining to polypeptide conjugates of drugs has been reviewed and the importance of this metabolic route in neonatal animals discussed.

Amino Acid Sequence↗
PubMed1984

Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in man.

Interindividual variation in the sulphoxidation of S-carboxymethyl-L-cysteine (750 mg p.o.) was investigated in 200 healthy volunteers. Nearly a 100-fold difference was observed between individuals with respect to the amount of sulphoxide metabolites detected in their 0-8 h urine (0.6 to 59.1% recovery). Such a difference was shown to be reproducible over several months in 40 subjects who spanned the entire range of capacities. Cumulative plots and maximum likelihood analysis of the distribution indicated that a bimodal model was most probable. Analysis of pedigree data obtained from 12 families suggested a genetic effect with overlying environmental influences.

Adolescent↗
PubMed1984

The metabolism of S-methyl-L-cysteine in man.

The excretion and metabolism of radiolabelled S-methyl-L-cysteine (150 mg orally) was studied in three male volunteers. The major route of excretion was the urine with 55.9% of the administered radioactivity being voided over three days (33.3% during the first 24 h). Faecal excretion was relatively unimportant (c. 1.4%). The remaining radioactivity was either slowly excreted in the urine over the next 21 d (35S-labelled compound) or exhaled (14C-labelled compounds). Metabolism occurred via the pathways of S-oxidation, N-acetylation and deamination. Extensive degradation of the molecule was observed with the production of large amounts of inorganic sulphate and CO2. The options for the sequence of metabolic degradation of the amino acid derivative are discussed.

Acetylation↗
PubMed1984

D-Penicillamine induced toxicity in rheumatoid arthritis: the role of sulphoxidation status and HLA-DR3.

Sulphoxidation of carbocysteine, a drug structurally similar to D-penicillamine, displays a skewed distribution within a population. In 66 patients with rheumatoid arthritis (RA) a significant association between impaired sulphoxidation and toxicity (p less than 0.001) was found; HLA-DR3, although associated with toxicity (p less than 0.05), appeared to be an independent risk factor of most importance in the group with extensive sulphoxidation. The relative risk of toxicity in a patient possessing either DR3 or impaired sulphoxidation was 25. The prevalence of poor sulphoxidizers within this group of RA patients was increased compared to that in a previous population study and requires further investigation. Our findings explain a number of the toxic phenomena associated with D-penicillamine administration in RA.

Adult↗
PubMed1983

The metabolism of S-carboxymethyl-L-cysteine in man: isolation of an ester glucuronic acid conjugate from urine.

A conjugate isolated from urine of human volunteers after an oral dose of S-carboxymethyl-L-cysteine was characterized as a carboxylic acid ester glucuronide. Of the 166 volunteers investigated, 61 gave no detectable drug glucuronide (less than 0.5% administered dose); the remaining 105 showed a unimodal distribution of drug glucuronide excretion accounting for 0.5-11.5% (mean 4.1%, median 3.4%) of the total dose recovered in the 0-8 h urine. No significant variation in subject age, sex or urinary pH was observed between the two groups, but those not excreting urinary glucuronide had significantly higher 0-8 h urine volumes (P less than 0.001), although notable exceptions occurred.

Adult↗
PubMed1983

The development of drug-metabolizing enzymes in the neonatal guinea-pig.

In the guinea-pig, drug-metabolizing enzyme activities, with the exception of glucuronylation and possibly hydrolysis, tend to develop more rapidly after birth than in the other commonly investigated rodent species. This anomalous nature of the guinea-pig during its neonatal period should be borne in mind when assessing drug-metabolizing capacity and the potential toxic effects of chemicals in developing animals.

Aging↗
PubMed1982

A comparison of the metabolism and elimination of benzanilide and salicylanilide in the rat.

1. The metabolism and elimination of benzanilide and salicylanilide in rats were compared. 2. For both compounds, greater than 70% dose was excreted in urine with 20% in faeces, in 3 days. 3. With [14C]benzanilide and [14C]salicylanilide, 40% and 35% respectively of the 14C was excreted in the bile in 24 h. 4. Benzanilide was metabolized to 4'-hydroxybenzanilide (24%), 2-hydroxybenzanilide (salicylanilide, 19%) and 2'-hydroxybenzanilide (13%), with small amounts of 4-hydroxybenzanilide. 5. Salicylanilide was excreted unchanged (56%) with small amounts of the 5-hydroxy and 4'-hydroxy-derivatives. 6. All metabolites were present as glucuronide conjugates; the free aglycones were not found.

Anilides↗
PubMed1982

The metabolism of [14C]cimetidine in man.

1. The excretion and metabolism of [2-(14)C]cimetidine (500 mg orally) was studied in five male volunteers. 2. Over 70% of the 14C was excreted in the urine after 24 h by all individuals with 5% in the faeces; 97% being recovered in total after three days. 3. Unchanged cimetidine was the largest urinary component (63%), followed by a polar conjugate tentatively identified as cimetidine N'-glucuronide (24%). Smaller amounts of the oxidized metabolites, cimetidine sulphoxide and 5-hydroxymethylcimetidine, together with the hydrolysis products, cimetidine guanylurea and cimetidine guanidine, were also observed. 4. Cimetidine and its sulphoxide were identified in faecal samples. Anaerobic incubations of cimetidine or cimetidine sulphoxide with faecal homogenates showed that reduction was the predominant reaction under these conditions. 5. Studies in one individual over a wide dose range (0.5 mg to 1.5 g orally) showed little variation in excretory profile or metabolic spectrum.

Administration, Oral↗
PubMed1981

A comparison of the in vivo metabolism of phenothiazine and promazine in the neonatal guinea pig.

The in vivo metabolism of promazine and phenothiazine was studied in neonatal guinea pigs aged 1-21 days. Urinary metabolites were estimated for both compounds; marked fluctuations with age were noted, some values being greater than those found for adult animals. Unconjugated phenol (C-oxidation products) levels were very low, although glucuronide excretion was always present; glucuronyl transferase activity did not appear to be limiting, and was present as early as 1 day after birth. Peak sulphoxide excretion showed no correlation with output of other metabolites, suggesting that S- and C-oxidation are not directly linked.

Aging↗