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G C Bolton

Publications and source records attributed to G C Bolton.

9 recordsLinked to original sources
PubMed1996

The fate of a thiazolidinedione antidiabetic agent in rat and dog.

1. The fate of [14C]BRL 49653C, a novel thiazolidinedione antidiabetic agent, has been studied following oral administration to the rat and dog. 2. Clearance was almost exclusively by metabolism, with only small amounts of unchanged BRL 49653 being excreted by either species. 3. Phase I metabolism resulted in ring hydroxylation, N-demethylation and oxidative removal of the pyridinylamino function to yield a phenoxyacetic acid derivative. 4. Sulphation of phase I metabolites occurred in both species, but glucuronidation was only observed in the rat. 5. The parent compound was the major circulating component in both species at early times, but at later times sulphate conjugates of phase 1 metabolites were predominant.

Animals↗
PubMed1986

The disposition of clavulanic acid in man.

Following oral administration of potassium 14C-clavulanate to four human subjects, at least 73% of the radioactive dose was absorbed. The mean absolute bioavailability was 64%. Absorption was rapid with peak plasma concentrations of radioactivity and clavulanic acid (2-6 micrograms/ml) occurring between 45 min and three hours after dosing. Values for the volume of distribution at steady-state and terminal half-life of clavulanic acid in the plasma were 12.01 and 0.8 h respectively. Following intravenous administration of clavulanic acid to the same subjects, the clearance, and volume of distribution at steady-state were 0.21 l/min, and 12.01, respectively. Clavulanic acid was the major radioactive component present in 0-24 h urine following oral dosing (23% of the dose). The two major metabolites were 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid (15% of the dose) and 1-amino-4-hydroxybutan-2-one (8.8% of the dose). Clavulanic acid and 1-amino-4-hydroxybutan-2-one were the major components in plasma following oral administration (52 and 21% of plasma radioactivity respectively at two hours after dosing). The major route of excretion of radioactivity following oral administration was via the urine (73% of the dose). Most of this radioactivity was excreted in the first 24 h after dosing (68% of the dose). The renal clearance of clavulanic acid was 0.1 l/min. Elimination of radioactivity also occurred via the expired air (17% of the dose) and the faeces (8% of the dose).

Chromatography, Thin Layer↗
PubMed1984

Absorption, metabolism and excretion studies on clavulanic acid in the rat and dog.

At least one third of an oral dose of sodium [G-14C]clavulanate was absorbed by rat and dog. Excretion of radioactivity was rapid in both species. In addition to urinary and faecal excretion of radioactivity, appreciable elimination of 14CO2 occurred, particularly in the rat. This was produced in part by the action of the gut microflora. In the rat, only a small proportion of the radioactive dose was secreted in the bile. The major metabolite in urine was identified as 1-amino-4-hydroxybutan-2-one. Clavulanic acid was also a major component in urine.

Animals↗
PubMedDate not supplied

The metabolic disposition of [14C]pivhydrazine, [14C]mebanazine, and [14C]benzylhydrazine in the rat.

The hydrazine drugs, [14C]pivhydrazine and [14C]mebanazine and the related compound [14C]benzylhydrazine were readily absorbed from the rat gut and the radioactivity was excreted mainly in urine. The major urinary metabolite of pivhydrazine and benzylhydrazine was [14C]hippuric acid, whereas mebanazine was shown to be excreted largely unchanged. Biliary excretion (21 and 24%, respectively) of radioactive material was observed after administration of [14C]pivhydrazine and [14C]mebanazine to bile duct-cannulated rats but only small amounts (approximately 3%) were excreted in bile after [14C]benzylhydrazine administration. The major biliary metabolites of pivhydrazine and mebanazine are acid-labile conjugates, possibly N-glucuronides. In vitro studies with rat liver homogenate suggest that benzylhyrazine may be an intermediate in the metabolism of pivhydrazine. The distribution of radioactivity in the rat 7 days after the administration of [14C]pivhydrazine and [14C]pivhydrazine and [14C]mebanazine is described.

Animals↗