[On the toxicology of carbromal. I. Estimation of carbromal and its hypnotically active metabolites in rats and humans (author's transl)].
To analyze the toxic effects of carbromal it was necessary to have information on the concentrations of carbromal and of its metabolites in the organism. This information can be obtained by a simple method based on gaschromatography that allows rapid, specific, sensitive and quantitative estimation of carbromal and of its hypnotically active metabolites bromoethylbutyramide and ethylbutyrylurea. Employing different detectors (flame ionisation or electron capture detector) the limit of detection for carbromal and of its two metabolites was 2-3 nmoles/g of tissue. The method was used to study in rats the absorption and elimination of carbromal including biotransformation of carbromal to bromoethylbutyramide and ethylbutyrylurea. Both metabolites, significant amounts of which were found in serum and brain, distribute evenly between serum and brain as does carbromal. Both metabolites were detectable in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of 1 g (4.2 nmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3-4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2-3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of these metabolites were recorded 4-5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal.
[On the toxicology of carbromal. I. Estimation of carbromal and its hypnotically active metabolites in rats and humans (author's transl)]. To analyze the toxic effects of carbromal it was necessary to have information on the concentrations of carbromal and of its metabolites in the organism. This information can be obtained by a simple method based on gaschromatography that allows rapid, specific, sensitive and quantitative estimation of carbromal and of its hypnotically active metabolites bromoethylbutyramide and ethylbutyrylurea. Employing different detectors (flame ionisation or electron capture detector) the limit of detection for carbromal and of its two metabolites was 2-3 nmoles/g of tissue. The method was used to study in rats the absorption and elimination of carbromal including biotransformation of carbromal to bromoethylbutyramide and ethylbutyrylurea. Both metabolites, significant amounts of which were found in serum and brain, distribute evenly between serum and brain as does carbromal. Both metabolites were detectable in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of 1 g (4.2 nmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3-4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2-3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of these metabolites were recorded 4-5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal.