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Biomedical subjects

L F Chasseaud

Publications and source records attributed to L F Chasseaud.

At least 109 records · Page 6Linked to original sources
PubMed1980

The metabolic fate of Sormodren (bornaprine hydrochloride) in animals and humans.

1. Single oral doses of the anticholinergic drug [14C]Sormodren to rats (1 mg/kg), dogs (0.3 mg/kg) and humans (0.03 mg/kg) were well absorbed. Excreted in urine and faeces were means of 31 and 70%, 53 and 39%, and 78 and 4% in rats, dogs, and humans, respectively, during five days: excretion was prolonged and still incomplete at five days in humans. 2. Peak plasma levels of 14C (scaled for dose) were generally reached within 1-2 h after oral doses in rats, 49 (ng/ml)/(mg/kg), dogs 290 (ng/ml)/(mg/kg) and humans 410 (ng/ml)/(mg/kg), and declined with half-lives of approx. 5, 12 and 30 h, in these species respectively. Repeated oral doses of [14C]Sormodren to dogs resulted in some accumulation of 14C in the plasma. 3. Tissue concn. of 14C in dogs were generally higher than those in rats, particularly in the brain, lungs and eyes. The tissue distribution of 14C in rats and dogs was consistent with that of a compound readily eliminated by both renal and hepatic routes. 4. Basic metabolites in dog and human, urine and plasma were investigated using a combination of h.p.l.c. and g.l.c.-mass spectrometry. Unchanged Sormodren was not detected in the dog samples and was only a minor component in human urine and plasma. Some metabolites were present as conjugates. 5. A basic extract of enzyme-hydrolysed dog urine (5 mg/kg dose) contained 42% of the urine 14C. The major metabolites in this fraction were identified as three isomers of monohydroxy-N-desethyl-Sormodren and three isomers of monohydroxy-Sormodren, resulting from hydroxylation in the bicyclic ring. The positions of oxidation were not determined. A similar extract from dog urine (0.3 mg/kg dose) contained 26% of the urine 14C and the major metabolites were identified as isomers of monohydroxy-N-desethyl-Sormodren. 6. A basic extract of enzyme-hydrolysed human urine (0.03 mg/kg dose) contained 23% of the urine 14C. The unchanged drug was only a minor component and most of the radioactivity was associated with five isomers of monohydroxy-Sormodren, hydroxylation having occurred in the bicyclic ring. 7. Basic extracts of dog and human plasma only contained about 10% of the plasma 14C. Metabolites were chromatographically similar to the hydroxylated metabolites identified in the corresponding urine samples.

Adult↗
PubMed1980

The effect of caffeine on the absorption of 3H-dihydroergocryptine (DHEC) in the rat.

1. Following single oral doses of 3H-dihydroergocryptine (DHEC) to rats, most of the absorbed radioactivity was excreted in the bile, 18.5% +/- 3.2 SD after dosing with 3H-DHEC (0.1 mg/kg) and caffeine (1 mg/kg), and 15.1 +/- 4.6 SD after dosing with 3H-DHEC (0.1 mg/kg) alone. The exception data indicated that about 25% of a single oral dose of 3H-DHEC was absorbed. 2. During 7 h after the last of daily oral doses for 7 days, plasma concentrations of radioactivity were consistently significantly greater (P < 0.001 to < 0.01) in rats dosed with 3H-DHEC (0.1 mg/kg) and caffeine (1 mg/kg) than in those dosed with 3H-DHEC (0.1 mg/kg) alone. The extent of bioavailability of radioactivity was also signficantly greater during this time (P < 0.01) and during 24 h (P < 0.05) after the last of repeated oral doses of 3H-DHEC and caffeine than after 3H-DHEC alone.

Animals↗
PubMed1979

High-performance liquid chromatographic determination of the nitroimidazole azanidazole in human plasma and urine.

Azanidazole can be measured in plasma and urine by reversed-phase high-performance liquid chromatography employing UV detection. Peak mean plasma concentrations of azanidazole, of 267 ng/ml, occurred at 1.5 h after single oral doses to human subjects, and declined with a half-life of 0.8 h. Less than 0.5% of the dose was excreted in the urine as unchanged drug. Metabolites of azanidazole were also detected by the procedures used.

Chromatography, High Pressure Liquid↗
PubMed1978

High-performance liquid chromatographic determination of benzodiazepines in human plasma.

A simple and sensitive method for determination of benzodiazepines in plasma has been developed using high-performance liquid chromatography in a reverse-phase mode. The method is illustrated by application to plasma samples containing diazepam and N-desmethyldiazepam at concentrations which would be encountered during therapy, with limits of detection of 10 ng/ml and 2 ng/ml for diazepam and N-desmethyldiazepam, respectively.

Chromatography, High Pressure Liquid↗
PubMed1978

Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. II. The disposition of [14C] LAS after oral or subcutaneous administration.

The disposition of radioactivity has been studied after administration of single and repeated oral or subcutaneous doses of [14C] LAS to rhesus monkeys. After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 h. Means of 71.2% and 23.1% of the dose were excreted in the urine and faeces respectively during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and faeces respectively during 5 days, mostly during the first 24 h. After single oral doses of 30, 150 and 300 mg/kh peak plasma concentrations, at 4 h in all cases, were very similar representing 34, 41 and 36 micrograms/ml respectively. After single subcutaneous doses of 0.1, 0.5 and 1 mg/kg, peak plasma concentrations increased almost proportionately and represented 0.16, 0.72 and 1.13 micrograms/ml respectively. During 7 consecutive daily oral (30 mg/kh/day) or subcutaneous (1 mg/kg/day) doses, there was no accumulation of radioactivity in plasma. Mean peak concentrations and biological half-lives were similar after the first and seventh doses. After 7 doses of [14C]LAS, there was no localisation of radioactivity in any tissue. No unchanged LAS was detected in urine samples after oral or subcutaneous doses. About 5 major radioactive components were detected in urine extracts; all were apparently more polar than LAS, but were not sulphate or glucoronide conjugates.

Administration, Oral↗
PubMed1978

Plasma concentrations of isosorbide dinitrate after administration of increasing doses of a sustained-release formulation to human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after administration of increasing doses in the range 20--100 mg as sustained-release tablets (Isoket retard) containing 20 mg to human subjects. Means of peak concentrations of 4.2 ng/ml, 13.1 ng/ml, 20.7 ng/ml, 36.8 ng/ml, and 34.9 ng/ml were measured after doses of 20 mg, 40 mg, 60 mg, 80 mg and 100 mg, respectively. In the plasma of individual subjects, peak concentrations of isosorbide dinitrate increased in proportion to the dose administered. Areas under the plasma isosorbide dinitrate concentration-time curves also increased in proportion to the dose administered. Bioavailability parameters were better correlated to the dose over the range 20--60 mg than over the range 20--100 mg.

Adult↗