Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CARBROMAL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

[On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)].

Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide.

Adult↗
PubMed1976

[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.

Adult↗
PubMed1977

[On the toxicology of carbromal. II. Pharmacokinetics of carbromal and its hypnotically active metabolites in the rat (author's transl)].

Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5-8 fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with half-life of 3-4 h and 5-7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans.

Administration, Oral↗
PubMed1978

[On the toxicology of carbromal. IV. Binding of carbromal and its hypnotically active metabolites to human plasma proteins (author's transl)].

The binding of carbromal and its metabolites bromoethylbutyramide and ethylbutyrylurea to human plasma proteins was investigated in vitro by use of Sephadex-gelfiltration, equilibrium dialysis and ultrafiltration. No differences appeared in the binding characteristics of human plasma and of human albumine. In a concentration range between 3.10-8 and 1.5.10-6 moles/ml about 40% of the carbromal, and in a concentration range between 3.10-8 and 1.10-5 moles/ml about 30% of the bromoethylbutyramide are bound to plasma proteins. Proteinbinding of ethylbutyrylurea was found to be less than 5%. The binding constants, Ka, to human albumine and the binding energies deltaF 0 were found to be in the range of 0.5--1.2.10(3) L/Mol and 1.7--4.4 kcal/Mol, respectively. Protein binding of carbromal, bromoethylbutyramide, their chlorinated analgous compounds, chloroethylbutyrylurea and chloroethylbutyramide, and of ethylbutyrylurea is strongly correlated to the partition coefficients of these compounds between n-octanol and water, indicating that the intensity of proteinbinding depends on the hydrophobic character of the substances tested.

Blood Proteins↗
PubMed1979

[Metabolism of carbromal during detoxication with combined hemoperfusion and hemodialysis (author's transl)].

Combined charcoal hemoperfusion and hemodialysis was performed on three occasions in two patients with severe carbromal intoxication. The concentration of carbromal, its organic metabolites and of bromide was determined in arterial blood before and after passage of the charcoal column and behind the dialyzer cartridge. Results show a rapid metabolic degradation of carbromal including cleavage of bromide. Besides carbromal and its main metabolite 2-brome-2-ethylbutyramide (=carbromide) debromised organic metabolites appear to be responsible for the severity of the intoxication. Bromide plays no role in the pathogenesis of acute intoxication. Carbromal and its organic metabolites are eliminated through a large surface dialyzer almost as effectively as with charcoal hemoperfusion. The effectivity of detoxication is enhanced by the combination of both procedures. Free bromide is not adsorbed at charcoal but is readily dialyzable. Values of carbromal, calculated out of bromide levels, do not correspond to directly measured blood levels. Treatment of carbromal intoxication with combined hemoperfusion-hemodialysis should be performed early in all severe, risky or otherwise complicated cases until the patients awakens.

Adolescent↗
PubMed1979

Bioassay of carbromal for possible carcinogenicity.

A bioassay for the possible carcinogenicity of carbromal was conducted using Fischer 344 rats and B6C3F1 mice. Carbromal was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species with the exception of 49 low dose male mice and high dose female mice. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of carbromal were, respectively, 2,500 and 1,250 ppm for rats and 2,500 and 1,250 ppm for mice. The compound was administered for 103 weeks to rats and for 78 weeks to mice. The period of compound administration was followed by an observation period of 1 week for rats and 26 weeks for mice. There was no significant positive associations between the concentrations of carbromal administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed for male rats and for females of both species and the mean body weight among dosed male mice was lower than that for controls, indicating that the concentrations of carbromal administered to the animals in this bioassay may have approximated the maximum tolerated concentrations. None of the statistical tests for any site in female rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. There was a significant positive association between the concentrations administered and the incidences of adrenal pheochromocytomas in male rats; however, the Fisher exact comparisons were not significant. Under the conditions of this bioassay, dietary administration of carbromal was not carcinogenic in Fischer 344 rats or B6C3F1 mice.

Journal Article↗
PubMed1977

[Investigations of carbromal metabolism (author's transl)].

Erythro-2-Brom-2-ethyl-3-hydroxybutyramide has been isolated from the urines of patients with Carbromal intoxications as well as from the urine of rat, mouse and dog treated with either Carbromal or with 2-Brom-2-ethyl-acetamide. The identification of the excreted and synthetized metabolite was carried out by means of IR, Mass and NMR spectroscopy. Along with the erythro-2-Brom-2-ethyl-3-hydroxybutyramide one other bromine containing compound was isolated after Carbromal application only, its mass spectrum and rel. RF values having the same characteristics as the synthetized erythro-2-Brom-2-ethyl-3-hydroxybutyrylcarbamide. However, the purification of this metabolite so far has not been successful.

Animals↗
PubMed1976

[Carbromal intoxication: influence of hemodialysis and hemoperfusion].

It has been demonstrated with an in vitro model that hemoperfusion through Amberlite XAD4 or coated charcoal containing cartridges eliminates carbromal and its ureid derivatives more efficiently than hemodialysis. The following clearancs were measured in vitro (blood flow: 200 ml/min): Coil dialyser (1 m2): 55-85 ml/min, charcoal hemoperfusion 100-125 ml/min, Amberlite XAD4 hemoperfusion: 200 ml/min. The data of one patient who had been hemoperfused after the ingestion of 35 g Carbromal with the Haemocol cartridge (SMith & Nephews) are depicted. Our results permit to draw the conclusion that hemoperfusion at this time is the most efficient means to eliminate Carbromal from intoxicated patients.

Charcoal↗
PubMedDate not supplied

Determination of meprobamate in pharmaceutical dosage forms also containing carbromal by liquid chromatography and indirect photometric detection.

In a pharmaceutical form also containing carbromal, meprobamate could not be quantified selectively by classical methods described in pharmacopoeias due to a significant interference from carbromal. Consequently, reversed-phase HPLC methods have been developed to separate the two active ingredients using indirect photometric detection to visualize and determine meprobamate which has very poor chromophoric properties. Different parameters influencing the sensitivity of the indirect response, such as the nature of the highly absorbing compound added to the mobile phase (the marker) as well as the methanol content and the pH of this phase, have been studied. Two chromatographic systems containing benzoic acid or cinnamic acid as the marker, have been optimized and validated. Good linearity and reproducibility have been obtained with both systems but the cinnamic acid method has the advantage that meprobamate and carbromal can be determined simultaneously at 273 nm.

Benzoates↗
PubMed1979

Nonthrombocytopenic purpura induced by carbromal.

A case of carbromal-induced purpura is described and the typical clinical features are presented. The diagnosis was confirmed by patch tests with 1 percent and 5 percent carbromal in propylene glycol and the positive results of a macrophage migration inhibitory factor test for carbromal. The rash gradually subsided following withdrawal of the drug.

Adult↗
PubMed1976

[Structure of bromine containing metabolites of carbromal (author's transl)].

Isolation of three bromine containing metabolites from human urine is described and their chemical structure is proved by comparison of their physical properties with those of synthetically prepared substances. 2-Bromo-2-ethyl-butyramide, a pharmacologically active product, is showed to be the most important bromine containing metabolite by volume. In 3-position hydroxylated metabolites of carbromal, 3-hydroxy-carbromal and 2-Bromo-2-ethyl-3-hydroxy-butyramide have same physical properties as the synthesized DL-threo--diastereomeres.

Bromine↗
PubMedDate not supplied

Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice.

1. The central depressant effects of bromvaletone, carbromal and six non-bromo analogues were compared in mice. 2. The chloro analogues of bromvaletone and carbromal were slightly less potent as central depressant agents than the bromo compounds. 3. The chloro analogue of bromvaletone had the greatest margin between central depressant and lethal doses. 4. Lipophilicity (octanol-water partition coefficient) did not provide a unifying relationship for potency within this group of eight acylureas. However, within each of the two subsets of compounds, a linear relationship was found between relative potency and lipophilicity.

Animals↗
PubMed1985

Acute and chronic intoxication with carbromal preparations.

An important number of acute intoxications can be ascribed to the abuse of, until now, non-prescription carbromal preparations. Prolonged use of these drugs also leads to chronic intoxication with bromide accumulation. The clinical features and treatment of three suicidal Obral overdoses and of two patients presenting with bromism are presented. Laboratory findings, from admission to recovery, consist of qualitative TLC and quantitative HPLC drug assays in body fluids and the determination in plasma of the two competing ions chloride and bromide. The high frequency of acute intoxications and carbromal induced bromism stresses the need to bring these preparations under prescription.

Acute Disease↗
PubMed1976

Studies on the polymorphism of carbromal.

Specimens of carbromal obtained by crystallization from various solvents were analyzed. After a 9-month storage period, the occurrence of three polymorphic forms (I, II and III) was ascertained. The metastable form III obtained by crystallization from dimethylformamide showed a reasonably high stability. Preliminary pharmacological tests revealed clear-cut differences in the therapeutic effect between a commercial specimen and the polymorphic modification III. The results presented here indicate the importance of polymorphism of carbromal for medicinal use.

Animals↗
PubMed1978

[Diethylpentenamide, a substitute for carbromal? (author's transl)].

Bromcarbamide-containing sleeping pills are frequently used in suicide attempts and cause severe, often fatal, intoxication. Since 1975, the chemically related drug diethylpentenamide had been available (in the German Federal Republic) without prescription. The authors report four cases of attempted suicide with the drug. The signs were similar to those after carbromal intoxication. There was severe respiratory depression, successfully treated by extracorporeal detoxication with combined haemoperfusion and haemodialysis. One patient developed acute pancreatitis as a complication.

Acetamides↗
PubMedDate not supplied

Colorimetric determination of bromisoval and carbromal.

New colorimetric procedure for determination of bromisoval and carbromal is based on the hydroxamation reaction and colour developing after addition of Fe(ClO4)3. The method is employed for the estimation of both compounds in substances and in tablets.

Bromisovalum↗