Thalidomid-Analoga, 5. Mitt.: Untersuchungen zum Metabolismus der Thalidomid-�hnlichen Verbindung K-2004

Pischek, Gertrude; Kaiser, E.; Koch, H.

doi:10.1007/bf00911290

Cited by 4 publications

(1 citation statement)

References 3 publications

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“…The lack of clinical data may be due to the relatively low stability of ester and amide linkages in vivo, so that, causing any shortening of an already brief assumption that high doses of taglutimide can induce drug metabolism enzymes, but the clinical significance of this findind remains uncertain in view of dose dependence (24) and species variation (7) with regard to enzyme induction. Duration of Narcosis (min) 30 lic fate of dicoumarol is still obscure, but ring hydroxylation is the most probable pathway, as found with other substituted coumarin derivatives (18), whereas the unsubstituted coumarin itself undergoes extensive ring opening in the rat (19); ii) investigations of taglutimide metabolism have revealed the presence of products of hydrolytical ring scission and glucuronic acid conjugation, but produced no evidence that taglutimide itself, or one of its metabolites, is a substrate of microsomal monooxygenases (20,21). By contrast, microsomal enzyme inducers are usually metabolized by the cytochrome P-450 enzyme system (7).…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative

Wiener

Krivanek

Tuisl

et al. 1980

European Journal of Drug Metabolism and Pharmacokinetics

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Pretreatment with taglutimide significantly decreased the plasma dicoumarol level and shortened the duration of hexobarbital-induced narcosis in rats. Furthermore, taglutimide pretreatment accelerated the in vitro metabolism of dicoumarol, hexobarbital, o-nitrophenyl acetate and procaine, but not of 3,4-benzypyrene, as assayed in the 10,000xg supernatant fraction of rat liver homogenate. No definite increase was observed in liver wet weight, nor in the amount of microsomal and total liver protein in comparison with the control values. No marked differences were found between the effects of short- (4-day) and long-term (17-day) pretreatment on any of the studied parameters. The changes in drug metabolism and liver protein observed after taglutimide pretreatment differed from those observed after pretreatment with either phenobarbital or 3,4-benzypyrene. Taglutimide, like other inducing agents, is lipophilic, but differs from them in not being a substrate of monooxygenases.

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Section: In Vitro Experimentsmentioning

confidence: 99%

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative

Wiener

Krivanek

Tuisl

et al. 1980

European Journal of Drug Metabolism and Pharmacokinetics

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Thalidomid‐Analoga, 8. Mitt.: Resorption, Elimination und Metabolisierung von K‐2004 beim Menschen

Koch

Pischek

Hitzenberger

1976

Archiv der Pharmazie

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Der zeitliche Verlauf des Blutspiegels und der Harnelimination der Gesamtaktivitit, der unvertinderten Stammverbindung l a und des Hauptmetaboliten l c nach peroraler Applikation von 200 mg der tritiierten Testsubstanz ,,K-2004", einem nichtteratogenen Abkommling des Thalidomids, wurde a n 4 mannlichen Probanden untersucht. Die biologischen Halbwertszeiten wurden fur die Cesamtaktivitat mit 42,6 h, fur l a mit 9,2 h und f~ l c mit 106,8 h berechnet. Rund 65 % der verabreichten Dosis werden mit dem Harn ausgeschieden. Absorption, Elimination, and Metabolism of K-2004 in ManThe time course of blood level and urinary elimination of the total activity, the unchanged parent mmpound l a and the main metabolite l c after oral application of 200 mg of the tritiated test compound "K-2004", a non-teratogenic congener of thalidomide, has been investigated in 4 male subjects. The biologic half-lives have been calculated as 42,6 h for the total activity, 9,2 h for l a and 1063 h for lc. About 65 % of the administered dose are excreted in the urine.

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Thalidomid‐Analoga, 9. Mitt. Blutspiegelverlauf und Organverteilung von Biglumid (K‐2004) bei der Maus

Pischek

Fiebrich

Koch

1977

Archiv der Pharmazie

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The distribution of the totalradioactivity in the blood, in various organs and tissues, and in the fetuses of mice after oral application of 140 mg/kg 3H-biglumide was determined, and the time course of the blood levels as well as the tissue concentrations in brain, liver, and kidney were measured. No appreciable accumulation of the compound and/or its metabolites takes place in any part of the organism. The calculated half-lives range between 0.28 and 0.40 h for the invasion and between 1.99 and 2.69 h for the elimination.Pharmakokinetische Untersuchungen tragen entscheidend bei zum Verstandnis der pharmakodynamischen Wirkungsweise eines neuen Arzneimittels. Der zeitliche Verlauf von Resorption und Elimination gibt AufschluB iiber das An-und Abfluten des Wirkstoffs, Art und AusmaB der Metabohvlerung informieren uber die jeweils vorhandene Mcnge an aktiven Wirkstoffmolekiilen oder gegebenenfalls von toxischen Metaboliten in der Siophase.

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Thalidomid-Analoga, 5. Mitt.: Untersuchungen zum Metabolismus der Thalidomid-�hnlichen Verbindung K-2004

Cited by 4 publications

References 3 publications

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative

Thalidomid‐Analoga, 8. Mitt.: Resorption, Elimination und Metabolisierung von K‐2004 beim Menschen

Thalidomid‐Analoga, 9. Mitt. Blutspiegelverlauf und Organverteilung von Biglumid (K‐2004) bei der Maus

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