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Biomedical subjects

G G Skellern

Publications and source records attributed to G G Skellern.

At least 55 records · Page 3Linked to original sources
PubMed1983

The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease.

1 Bumetanide (1 mg) was given orally and intravenously to a group of patients with chronic renal failure (n = 6) and to another group with cirrhosis of the liver (n = 8). 2 The pharmacokinetics, using a two-compartment model, and the pharmacodynamics of the drug in these patients were compared with those previously obtained for normal subjects. 3 In the renal group serum bumetanide concentrations were higher than for the normal subjects and the terminal half-lives were significantly prolonged (P less than 0.001). A decreased whole body clearance was attributable to a low renal clearance of drug, the non-renal clearance being significantly increased (P less than 0.01). 4 For the patients with liver disease, serum bumetanide concentrations were higher than for the renal group, and the terminal half-lives were significantly further prolonged (P less than 0.001). Both non-renal and renal clearances were significantly reduced (P less than 0.001). 5 Absorption rates were not significantly altered in either group and the values of F (bioavailability) were 0.82 and 0.95 for the patients with renal disease and hepatic disease, respectively. 6 A poor pharmacodynamic response and a reduced bumetanide excretion rate were observed for the patients with chronic renal failure, whereas with hepatic disease normal bumetanide excretion rates were observed with an impaired diuretic response.

Administration, Oral↗
PubMed1983

Gas chromatographic determination of nicotine in human breast milk.

In this study, nicotine concentrations in the breast milk of lactating women were measured by gas chromatography. In one group of smokers, the concentrations measured were related to the number of cigarettes smoked earlier in the day. Low nicotine concentrations were found in the breast milk of nonsmokers exposed to a smoky atmosphere.

Chromatography, Gas↗
PubMed1982

The pharmacokinetics and pharmacodynamics of bumetanide in normal subjects.

The pharmacokinetics and pharmacodynamics of bumetanide (1 mg) administered either orally or intravenously were studied in a group of normal subjects using high-pressure liquid chromatography. A two-compartment model adequately fitted the intravenous data. Renal clearance (85 ml min-1) contributed 65% to the total elimination of bumetanide irrespective of whether a model-dependent or model-independent method was used. Oral administration of bumetanide elicited a greater and a more prolonged pharmacological response than did intravenous bumetanide. An attempt is made to relate the pharmacokinetics of the drug to its pharmacodynamics.

Administration, Oral↗
PubMed1981

Intrathyroidal iodide binding rates and plasma methimazole concentrations in hyperthyroid patients on small doses of carbimazole.

1 The effect of small doses of carbimazole on the binding rate constant of intrathyroidal iodide, plasma methimazole concentrations and circulating thyroid hormone concentrations in five hyperthyroid patients is presented. 2 In all patients there was a marked reduction in iodide binding with carbimazole doses as low as 5 to 10 mg daily. 3 In three patients little further reduction in the observed binding rate occurred with daily doses in excess of 10 mg despite progressive increases in plasma methimazole concentrations. 4 At the end of 4 weeks' treatment with 10 mg carbimazole daily, the reduction in thyroid hormone concentrations and clinical improvement were such as to suggest that this dose may be an effective starting dose in many patients.

Adult↗
PubMed1981

Peritoneal absorption of the antibacterial and antiendotoxin taurolin in peritonitis.

1 Taurolin metabolite plasma concentrations were measured in two groups of patient undergoing abdominal surgery, one group with peritonitis and the other without peritonitis, each group receiving taurolin by intraperitoneal instillation. 2 There was no significant difference in the area under the curves, for the two groups, for one of the metabolites. This would suggest that the absorption of taurolin was not modified in inflammatory conditions such as bacterial peritonitis.

Absorption↗
PubMed1981

The metabolism of [2-14C]methimazole in the rat.

1. The metabolism of [2-14C]methimazole was studied in Sprague-Dawley rats after a daily intraperitoneal dose of 17.6 mg/kg for three days. 2. 78.4% of the administered 14C was excreted in the urine; only 6.7% dose as methimazole. After extraction of the urine with chloroform and n-butanol, 47.5% of administered 14C remained in the urine. 3. Six solvent-extractable metabolites were isolated and characterized by t.l.c. and high-resolution mass spectrometry, as N-methylimidazole, S-methylmethimazole, 3-methyl-2-thiohydantoin, 1-methyl-2-thiohydantoic acid, N-methylthiourea and a methylhydantoin.

Animals↗
PubMed1980

The pharmacokinetics of methimazole after oral administration of carbimazole and methimazole, in hyperthyroid patients.

1 Methimazole plasma concentrations were measured in two groups of hyperthyroid subjects after the oral administration of either carbimazole or methimazole. 2 With the HPLC method it was also possible to measure the concentration of a methimazole metabolite, 3-methyl-2-thiohydantoin in one patient. 3 Large interindividual differences were observed, especially within the carbimazole group. 4 Incomplete absorption of carbimazole could explain particular high apparent volumes of distribution and apparent clearances.

Administration, Oral↗
PubMed1980

The pharmacokinetics of methimazole in pregnant patients after oral administration of carbimazole.

1 A high performance liquid chromatographic (HPLC) method was used to study the pharmacokinetics of methimazole after oral administration of carbimazole to women in various stages of pregnancy. 2 In one patient it was possible to conduct the study in the first and third timesters: there was an appreciable increase in the apparent clearance of methimazole. 3 Based on the assumption of complete absorption and hydrolysis of carbimazole to methimazole the mean apparent clearance was found to be significantly higher in pregnant patients receiving 10 mg carbimazole than in non-pregnant patients receiving the same dose.

Administration, Oral↗
PubMed1979

Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients.

Adult↗
PubMed1978

The application of HPLC to the determination of some 1,4 benzodiazepines and their metabolites in plasma.

1 A high pressure liquid chromatographic (HPLC) assay has been developed for the measurement of chlordiazepoxide and its metabolites, N-desmethylchlordiazepoxide and demoxepam in microgram concentrations in human plasma. 2 Another metabolite was detected in appreciable amounts in the plasma from patients receiving high doses of chlordiazepoxide after the first 3 days of treatment. 3 Preliminary studies would indicate that this metabolite is N-desmethyldiazepam. 4 A modified HPLC system, using a microparticulate column was developed to separate N-desmethyldiazepam from chlordiazepoxide and its other metabolites in plasma.

Benzodiazepines↗
PubMed1977

Identification of 3-methyl-2-thiohydantoin, a metabolite of carbimazole, in man.

1. Classical and high-pressure liquid chromatographic separations were devised for the separation and isolation of the metabolite 3-methyl-2-thiohydantoin from the urine of patients receiving carbimazole orally. 2. 3-methyl-2-thiohydantoin was identified by comparing its absorption and mass spectral properties with authentic material. 3. 3-methyl-2-thiohydantoin was also detected in the plasma of patients receiving methimazole intravenously.

Carbimazole↗