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Biomedical subjects

D H Chatfield

Publications and source records attributed to D H Chatfield.

9 recordsLinked to original sources
PubMed1979

The metabolism of isamoxole in the rat and guinea-pig.

1. The absorption, metabolism and excretion of isamoxole, (2-methyl-N-butyl-N-(4-methyloxazol-2-yl)propanamide), a compound with anti-allergy properties, has been studied in the rat and guinea-pig. 2. The compound was well-absorbed by both species after oral doses of 50 to 150 mg/kg. It underwent extensive first-pass metabolism in the liver, and was excreted as a mixture of metabolites, predominantly in the urine, within 48 h. 3. Three major routes of metabolism were involved, namely deacylation, oxidative ring scission and alkyl oxidation. 4. A major plasma and urine metabolite was 1-butyl-3-(1-carboxyethyl)urea, and this was accompanied by low levels of its cyclized product 3-butyl-5-methylhydantoin.

Animals↗
PubMed1978

Determination of benoxaprofen [2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid, LRCL 3794] in biological fluids.

Benoxaprofen, a novel anti-inflammatory compound, is efficiently (greater than 95%) extracted from plasma and urine in the pH range 1 to 5 into either chloroform or ether. The compound is determined either by UV spectroscopy or by gas-liquid chromatography of the methyl ester (formed by reaction with diazomethane) on a column of 3% of silicone gum E-301 on DCMS-treated Chromosorb W, with detection by flame ionisation (limit 0.3 microgram/ml) or electron capture (limit 0.01 microgram/ml). For rapid routine use, the UV method (limit ca. 5 microgram/ml) gives good agreement with the specific methods.

Animals↗
PubMed1978

Determination of isamoxole (N-butyl-N-(4-methyloxazol-2-yl)-2-methylpropanamide, LRCL 3950) in plasma by selected ion monitoring using a stable isotope internal standard.

A selected ion monitoring method for the estimation of an anti-allergy compound isamaxole (N-butyl-N-(4-methyloxazol-2-yl)-2-methylpropanamide, LRCL 3950) in plasma has been developed. The method uses a stable analogue containing nine deuterium atoms as internal standard. The assay is sensitive to 2 ng ml-1 plasma and has been used to examine plasma levels of isamoxole after doses of the compound to animals and man.

Animals↗
PubMed1978

Disposition and metabolism of benoxaprofen in laboratory animals and man.

1. The absorption, distribution, metabolism and excretion of benoxaprofen, a novel anti-inflammatory compound, has been studied in the dog, mouse, rat, rabbit, rhesus monkey and man. 2. Benoxaprofen was well absorbed after oral administration of doses of 1 to 10 mg/kg in all six species. Only unchanged drug was detected in plasma. It was extensively bound to plasma proteins, the highest binding occurring in man (99.8%) and rhesus monkey (99.6%). 3. Species differences were observed in the plasma elimination half-life, the longest being in man (33 h). The rat and mouse also had high values (28 and 24 h respectively) whereas in the other species, values were less than 13 h. 4. After an oral dose of [14C]benoxaprofen (20 mg/kg) to female rats, tissue concn. was highest in liver, kidney, lungs, adrenals and ovaries. Tissue distribution in the pregnant rat was identical to the normal female. The compound was found in the foetus but at a concn. lower than in all maternal organs. 5. There was a marked species difference in the route of excretion. In man, rhesus monkey and rabbit, excretion in the urine was a major route, whilst biliary--faecal excretion was the only effective route in the rat and dog. 6. No major metabolic transformation of benoxaprofen was observed. Man and dog excreted the compound predominantly as the ester glucuronide whereas the rat, mouse, rabbit and rhesus monkey excreted a large proportion of the dose unchanged.

Administration, Oral↗
PubMed1977

Pharmacokinetic studies with benoxaprofen in man: prediction of steady-state levels from single-dose data.

1 Plasma levels of benoxaprofen were measured in eight subjects 2-168 h after a single oral dose of 100 mg. Pharmacokinetic parameters were estimated by the NON-LIN computer programme using the two-compartment open model. Mean half-lives of absorption, distribution and elimination were respectively 0.4, 4.8 and 37.6 hours. Volumes of distribution were 6.8 and 3.2 litres for the central and peripheral compartments respectively. 2 Eleven subjects in groups of three or four were given 25 mg/day, 50 mg/day or 100 mg two times daily for 11 days. Their plasma levels were compared with those predicted from the above parameters, which were adjusted for individual body weights and elimination half-lives. Steady-state plasma levels were predicted in each case, and a resonable degree of accuracy (mean 91%) achieved. 3 There was no tendency for observed and predicted levels to diverge as the dose was increased, and there was no evidence of any change in the disposition of benoxaprofen on repeated dosing. 4 The pharmacokinetic parameters were used to predict steady state plasma levels for various dosage regimens.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1977

Preliminary studies of absorption and excretion of benoxaprofen in man.

1 Benoxaprofen is a new acidic anti-inflammatory compound which was well absorbed after oral administration to man. 2 Single doses of 100, 200 and 400 mg produced mean peak concentrations in the plasma of 13.0, 33.5 and 45.3 microgram respectively, and the plasma half-life of the compound was between 30 and 35 hours. 3 Multiple dosing with 25 and 50 mg every 24 h achieved an equilibrium conentration in the plasma after 6-8 days, while dosing with 100 mg every 12 h enabled equilibrium to be reached in 3-6 days. Plasma concentrations between 35 and 45 microgram/ml were achieved by giving 100 mg doses every 12 hours. 4 Absorption of benoxaprofen was delayed when the drug was given with food, but the total amount absorbed remained the same. 5 The effect of milling the material to small particle size (19 micron) was to increase the rate of absorption compared to that of unmilled material (58 micron). 6 Benoxaprofen was well tolerated by healthy male subject in the doses given.

Adult↗
PubMed1976

Disposition and metabolism of some nitrofurylthiazoles possessing antiparasitic activity.

1. The absorption, distribution and excretion of two 35S-labelled nitrofurylthiazole analogues have been investigated in rats and mice. The compounds are not well absorbed. Higher plasma and tissue levels are reached when more water-soluble analogues are administered. 2. Metabolic transformations of these two compounds and other membranes of the series include reduction of the nitro group, degradation of the furan ring and oxidation of the terminal alicyclic and aliphatic functions. 3. Metabolic cleavage of a morpholine ring to form an hydroxy-acid has been demonstrated for one member of the series.

Anaerobiosis↗