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Biomedical subjects

A Somogyi

Publications and source records attributed to A Somogyi.

At least 145 records · Page 8Linked to original sources
PubMed1980

[Absolute bioavailability of theophylline (Euphylline)].

The pharmacokinetics and bioavailability of theophylline have been investigated in eight healthy subjects following application of the drug in form of a tablet, a retard tablet (enteric-coated), and a suppository (Euphyllin) in comparison with an intravenous preparation. Peak plasma concentrations were measured 1.5 hours (tablet), 6 hours (retard tablet) and 4 hours (suppository) after drug administration, respectively. The absolute bioavailability was of th tablet 105 +/- 25%, of the retard table 81 +/- 23%, of the suppository 74 +/- 25%. The variations observed were primarily due to variations in the other pharmacokinetic parameters, only to a lesser extent to variable absorption of theophylline.

Adult↗
PubMed1980

[Bioavailability of cimetidine after partial gastrectomy (author's transl)].

Absorption characteristics of cimetidine were studied in 10 patients after Billroth I and 12 patients after Billroth II gastrectomy and compared with 9 patients without gastric disease. The onset of absorption after 400 mg cimetidine was identical in all groups, but peak plasma concentrations occurred somewhat (18%) later in B I and significantly (42%) later in B II patients (p less than 0.05). Plasma half life was not different between the 3 groups. The area under the plasma level curve as a measure for bioavailability was significantly increased in the two gastrectomy groups (17% and 23%, resp.). In addition, the duration of effective plasma concentrations above 0.5 microgram/ml was significantly prolonged in the two groups.

Biological Availability↗
PubMed1980

Effects of verapamil on P-R-intervals in relation to verapamil plasma levels following single I.V. and oral administration and during chronic treatment.

A close relationship between verapamil plasma concentration and effect on P-R interval could be established both after single i.v. and oral administration and during chronic oral treatment. After i.v. administration a linear relationship between verapamil plasma concentration and delta P-R (y=x (0.74) + 1.8) with a small between subject variation in the slope of the regression (%coefficient of variation 18.7, range 0.71-1.10) was observed. The slope of the oral plasma concentration response regression (y=x (0.33)-3.0) was statistically significantly (p less than 0.05) less than the slope of the i.v. plasma level response regression. Interindividual variation in the slope was most pronounced (range 0.13 to 0.47). On average two to three times higher verapamil plasma levels were required after oral administration in order to produce the same increase in delta PR as after intravenous administration. The most plausible explanation for the different slopes of the plasma level response regression seems to be stereo-selective presystemic elimination. Since after oral administration the plasma level response curve is less steep than after i.v. administration this indicates that the more active l-isomer is preferentially metabolized during hepatic first-pass metabolism.

Administration, Oral↗
PubMed1979

Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

Animal Feed↗
PubMed1976

[Contemporary animal nutrition and its potential hazards to human health (author's transl)].

The growing challenge to secure wholesome food of animal origin in quantities sufficient to feed the ever increasing world population leads to the compelling need of search for new means to enhance animal production. Such an endeavor often involves the use of pharmacologically active agents. As new substances are continuously introduced into agriculture, the necessity clearly arises to reassess the requirements for the approval of compounds likely to appear in the food of man via the edible tissues of animals. Since a number of animal drugs and feed additives have been recently found to show carcinogenic potency, using examples from their own research, the authors discuss problems encountered while planning animal studies for the safety evaluation of chemicals. Among the most important factors to be reckoned with is the metabolism of the test substance. Most carcinogens require metabolic transformation in order to react with macromolecules and, thus, exert their biological action. Similarly, residues of many drugs in animal tissues appear to be various metabolites rather than the parent compounds themselves. At present, it is not known whether many chemical residues are simply stored in different compartments of the carcass as a result of their physico-chemical properties or whether they are covalently bound to vital macromolecules (e.g., nucleic acids). Hence, their biological significance is not quite clear. The enzyme system which metabolizes numerous drugs, pesticides, as well as other endogenous and exogenous substrates is responsible for both the activation and detoxification of carcinogenic chemicals. The delicate balance between these two processes of opposing toxicological consequence is determined by genetic and environmental factors. Depending upon the metabolic profile of chemicals, certain compounds are carcinogenic in one animal species while not in others. The manipulation of their metabolism by physiological (e.g., stress) or pharmacological (e.g., inducers or inhibitors of microsomal enzymes) means can result in a profound change of various biological actions of chemicals (e.g., cytotoxicity, carcinogenicity, mutagenicity). To ascertain that potential toxicological hazards to human health by animal drugs and feed additives will be recognized during the phase of testing, appropriate test animals have to be selected with great care. It is indispensible that the metabolic break-down of the investigational substance proceeds via similar pathways in both test animals and the target species. This will assure that the same metabolites which, in the form of residues in food, man might be exposed to will have ample opportunity to exert their possible adverse effects to the experimental animals during a life-long feeding of the test substance. Therefore, it can, with a reasonable certainty, be assumed that, in experiments performed under such precautionary measures, toxico-pharmacological properties relevant to human safety evaluation will not remain undetected.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Inhibition of the acute toxicity and adrenocorticolytic effect of 7,12-dimethylbenz(a)anthracene by isopropylvaleramide and allylisopropylacetamide in the rat.

Isopropylvaleramide (IVA) and allylisopropylacetamide (AIA) inhibit hemorrhagic adrenocortical necrosis and mortality caused by 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats. Unlike their effect on hepatic microsomal cytochrome P-450, the anti-DMBA action of these compounds does not depend on the presence of the reactive allyl group in the molecule. Similarly, related barbiturates, regardless of whether they contain, like AIA, an allyl group and consequently destroy cytochrome P-450 (secobarbital and aprobarbital) or have, like IVA, saturated side chains and therefore do not effect the microsomal hemoprotein (pentobarbital and phenobarbital), proved ineffective in preventing both adrenal damage and death caused by DMBA. Hence, the protective action of IVA and AIA cannot be attributed to the destruction of the microsomal enzyme system responsible for the activation of DMBA. The toxicity of another carcinogen, dimethylnitrosamine, which also requires metabolic activation by microsomal enzymes, is not influenced by either IVA or AIA. IVA, which counteracts the adrenocorticolytic action of DMBA when given prior to, simultaneously with, or even after this carcinogen, has no discernible effect on hydrocarbon metabolism in vivo or in vitro. IVA is one of the most powerful inhibitors of the acute toxicity of DMBA. It has the simplest aliphatic structure and the smallest molecule among protectors of the adrenals against hydrocarbon-induced damage; its mechanism of action awaits further elucidation.

9,10-Dimethyl-1,2-benzanthracene↗