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L F Chasseaud

Publications and source records attributed to L F Chasseaud.

At least 91 records · Page 5Linked to original sources
PubMed1981

High-performance liquid chromatographic determination of lorazepam in monkey plasma.

A simple, sensitive and selective method for the determination of lorazepam in monkey plasma has been developed using high-performance liquid chromatography in a reversed-phase mode. The limit of detection for lorazepam in plasma is about 2 ng/ml. The method has been applied to plasma samples obtained from cynomolgus monkeys after oral doses of 0.15 mg/kg and intravenous doses of 0.05 mg/kg of lorazepam. In this species, mean peak plasma concentrations of 12 ng/ml occurred at 2 h after oral dosing and declined with a half-life of 2,5 h; the mean terminal half-life after intravenous dosing was 1.4 h.

Animals↗
PubMed1981

Pharmacokinetics of isosorbide dinitrate in rhesus monkey, cynomolgus monkey, and baboon.

At 2 min after intravenous injection of isosorbide dinitrate (1 mg/kg), mean plasma drug concentrations were 565 +/- 66 (SD), 586 +/- 43, and 1572 +/- 253 ng/ml in the rhesus monkey, cynomolgus monkey, and baboon, respectively. Following a relatively short distribution phase, mean plasma concentrations declined with half-lives of 62, 23, and 24 min in these three species, respectively. The time course of plasma concentrations could be described by a two-compartment open model, although a one-compartment open model was adequate for obtaining some pharmacokinetic parameters. Statistically significant differences among the species were observed in areas under the plasma concentration-time curves, plasma half-lives, and volumes of distribution. The pharmacokinetics kinetics of isosorbide dinitrate in baboons most closely resembled those in humans.

Animals↗
PubMed1981

Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey.

The pharmacokinetics of antipyrine (phenazone) in 3 species of non-human primate have been evaluated following its intravenous administration at a dose level of 92 mg/kg. Mean peak plasma concentrations of antipyrine of 132, 137 and 155 microgram/ml in the rhesus monkey, the cynomolgus monkey and the baboon respectively were not observed until 5 min after intravenous injection. Thereafter, concentrations declined with an apparent half-life of elimination of 1.5-2 h. The time-course of plasma antipyrine concentrations was adequately described by a one-compartment open model and no notable differences in pharmacokinetic parameters utilising a 2-compartment open model were observed. Antipyrine was mainly distributed in total body water. The mean volume of distribution was equivalent to 88, 73 and 66% of body weight in rhesus monkey, the cynomolgus monkey and the baboon, respectively. An analysis of variance of volumes of distribution, apparent half-lives of elimination and systemic clearances showed that there was a statistically significant species-related difference in systemic clearance (P less than 0.05) and volumes of distribution (P less than 0.01) which were lower in the cynomolgus monkey than in the other 2 species. The pharmacokinetics of antipyrine in the non-human primate are more similar to those of other laboratory animal species than to those of humans.

Animals↗
PubMed1981

Factors affecting induction of lung aryl hydrocarbon hydroxylase in rats exposed to cigarette smoke.

Induction of lung aryl hydrocarbon hydroxylase (AHH) activity has been studied in rats following their exposure to different regimes of cigarette smoke produced from tobacco and the tobacco substitute NSM. The rate of induction of AHH was maximal during the first 3 days of exposure to tobacco smoke. The frequency of exposure to tobacco smoke was apparently more important in influencing induction of AHH than was the duration of the exposure. After cessation of exposure to smoke, AHH activity declined to control levels within about 3 days. Tobacco smoke was a more potent inducer of AHH than was smoke from NSM. Measurement of AHH may provide a useful means of assessing whether animals involved in toxicity studies of smoking materials inhale sufficient total particulate matter to provoke a biological response, such as induction of AHH.

Animals↗
PubMed1981

The metabolic fate of 3[H]econazole in man.

1. Following single oral doses of 3[H]econazole base (500 mg) to two human subjects, excretion of radioactivity was prolonged, and incomplete after five days (means of 40% and 27% dose in urine and faeces respectively). 2. Plasma concn. of unchanged econazole and total radioactivity attained peak values at approx. the same for each subject (1.5 - 3h), but the former declined much faster than the latter. Most of the 3H in early plasma samples was present as unchanged drug and extractable metabolites, but after 24h concn. of econazole were close to the limit of detection (0.04 ug/ml) and very little plasma 3H was extractable, whereas total 3H concn. were still measurable after five days (mean 1.54 ug/ml). Thus, plasma contained metabolites with much longer half-lives than econazole. 3. The main route of biotransformation of econazole in man involved multiple oxidation of the imidazole ring carbons followed by O-dealkylation and conjugation of the resulting alcohols, probably with glucuronic acid.

Administration, Oral↗
PubMed1980

Determination of the antispasmodic agent ethaverine in human plasma by high-performance liquid chromatography.

Ethaverine can be measured in the plasma of human subjects by reversed-phase high-performance liquid chromatography employing UV detection. The limit of detection was 2 ng/ml, and the precision was +/- 14, +/- 6 and +/- 2% at concentrations of 5, 25 and 50 ng/ml respectively. A peak mean plasma drug concentration of 20 ng/ml occurred at 1.5 h after single oral doses of a capsule formulation to human subjects, and declined with a half-life of 2.9 h.

Administration, Oral↗
PubMed1980

The absorption and excretion of the peripheral vasodilator 14C-mecinarone, (14C-6809 MD) in rat, dog and man.

Oral doses of the peripheral vasodilator mecinarone (6809 MD), administered as the 14C-compound, were well absorbed from the gastrointestinal tract of rats, dogs and humans. Much of the dose was excreted in 24 by rats and dogs, but more slowly by humans. In 5 days, rats, dogs and humans excreted in the urine and faeces respectively means of 3.3 and 95.9%, 13.2 and 80.3%, and 22.0 and 60.8%. The proportions of radioactivity excreted in urine and faeces after intravenous doses were similar to those after oral doses, means of 3.1 and 85.0% respectively by rats and 16.8 and 78.3% by dogs. Radioactivity present in the faeces was probably mainly excreted in bile; rats (n = 2) excreted a mean of 52.3, 19.8 and 3.9% in bile, faeces and urine after oral doses. Plasma concentrations of radioactivity after oral doses reached a maximum at 1 h in rats (mean 126 ng equiv/ml), at 1 to 2 h in dogs (mean 784 ng equiv/ml) and at 1.5 to 2 h in humans (mean 547 ng equiv/ml. Only a small proportion of this radioactivity (10-30%) represented unchanged drug. When "normalised" for dose/bodyweight differences, those levels were in the ratio 1 : 7 : 32 (rat less than dog less than man). Areas under plasma radioactivity concentration-time curves after oral doses to rats and dogs were about 25% and 53% respectively of those after corresponding intravenous doses. Only about 20% of the radioactivity in the plasma of dogs at 2 min after an intravenous dose represented unchanged drug. These data suggest that 6890 MD was probably rapidly biotransformed in rat, dog and man.

Administration, Oral↗
PubMed1980

Aspects of the metabolism of the peripheral vasodilator mecinarone (14C-6809 MD) in rat, dog and man.

The major proportion of oral doses of 14C-mecinarone was excreted in the faeces by rat, dog and man, and in all species the faecal metabolites were more polar than mecinarone and the O-desmethyl reference compounds. Rat faecal extracts contained two major components each accounting for about 30-40% of the radioactivity. Dog and human faecal extracts contained some mecinarone but also three major, more polar components, two of which corresponded to the rat metabolites. Rat bile contained three major components and dog bile two components. One of the components in both bile samples was shown to be a conjugate of O-desmethyl-mecinarone. Besides mecinarone human urine contained a component corresponding to the phenol resulting from 0-demethylation in the p-methoxycinnamoyl group. The same two compounds were also detected in human plasma. The two major components in rat and dog faecal extracts gave mass spectra identical to mecinarone and the p-hydroxycinnamoyl derivative (O-desmethyl-mecinarone). It is postulated that these thermally-labile metabolites were formed by nucleophilic addition of a substituent to the alpha, beta-unsaturated ketone. It has been demonstrated in vitro that mecinarone forms a glutathione conjugate. The metabolites may be compounds of this type where the glutathione moiety has been degraded in the gastrointestinal tract.

Animals↗
PubMed1980

The distribution excretion and biotransformation of p-dichloro[14C]benzene in rats after repeated inhalation, oral and subcutaneous doses.

1. Following repeated daily whole-body exposure (3 h/day) of rats to atmospheres containing p-dichloro[14C]benzene (10000p.p.m.), or administration of oral or subcutaenous doses (250 mg/kg/day), 24-h tissue concn. of 14C were similar and did not increase after six days dosing, but tended to decrease. 2. After repeated daily atmospheric exposures or oral doses, highest concn. of 14C occurred in fat, kidneys, liver and lungs. Concn. declined rapidly to near or below limits of detection (less than 0.2 p.p.m.) in plasma and tissues at 5 days. After similar subcutaneous doses, tissue concn. declined more slowly. 3. During five days after repeated dosing, most excreted 14C (91-97%) was in the urine. Little was excreted in faeces or expired air. Excretion was more prolonged following subcutaneous administration. After single doses to bile duct-cannulated animals, 46-63% of the excreted 14C was in the bile during 24 h. 4. The pattern of metabolites in urine and bile was similar after each route of administration although there were quantitative differences. Urine extracts contained two major 14C-components, namely a sulphate and a glucuronide of 2,5-dichlorophenol, representing 46-54% and 31-34% of the urinary 14C respectively. Two minor components were identified by mass spectrometry as a dihydroxydichlorobenzene and a mercapturic acid of p-dichlorobenzene. 5. The glucuronide of 2,5-dichlorphenol was the major 14C component in bile (30-42%).

Administration, Oral↗
PubMed1980

The metabolic fate of tizoprolique acid in baboons.

1. After oral administration of the anti-lipolytic drug [14C]tizoprolique acid (2-propyl-5-carboxyl[4-14C]thiazole), to baboons (60 mg/kg), the radioactivity was well absorbed and rapidly excreted. During 6 and 24 h respectively, 60 +/- 25% (S.D.) and 90 +/- 2% were excreted in the urine. 2. Plasma concn. of 14C reached a max. (182 +/- 65, range 85-221 micrograms equiv./ml) at 1-1.5 h after an oral dose, and declined rapidly with an apparent half-life of about 0.5 h. A mean of 77 +/- 7% of the 14C in peak plasma samples was bound to plasma proteins, somewhat less than that of [14C]tizoprolique acid (84 +/- 5%). 3. Tissue concn. of 14 C were highest in an animal killed at 0.5 h after an oral dose, but were lower than those in plasma in all tissues examined except the kidneys. 4. The major metabolite of tizoprolique acid was its glycine conjugate, which accounted for about 80% dose excreted in the 24 h urine. About 2% dose was excreted as unchanged drug. About 70% and 20% respectively of plasma 14C were associated with the unchanged drug and its glycine conjugate during the period 15 min to 4 h after dosing.

Absorption↗