Biomedical subjects
Publications and source records attributed to T J Woodage.
(R)-(-)-benoxaprofen is stereospecifically inverted to the (S)-(+)-enantiomer by rats and humans. The rate of inversion is much faster in rats (t 1/2 ca. 2.5 h) than in humans (t 1/2 108 h). Inversion in rats apparently does not occur in the liver, but can be brought about in vitro by an everted intestinal sac preparation, suggesting that the transformation takes place while passing through the gut wall.
The bioavailability of a single 300 mg dose of benoxaprofen was compared after rectal and oral administration in 5 subjects. The total absorption rectally from a suppository was 83% of that achieved orally from a capsule. Six further subjects took a 300 mg benoxaprofen suppository twice daily for 12 d. Steady state plasma levels (mean level 94 microgram/ml) were reached at about 120 h, while the elimination half-life for benoxaprofen was approximately 38 h in this study. The suppositories were well tolerated. The plasma levels obtained compared very favorably with theoretically expected levels and levels obtained after comparable oral doses.
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.
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.
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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.
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