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  • 1
    Electronic Resource
    Electronic Resource
    ISolation and identification of a sulfur-containing metabolite of spironolactone from human urine
    Amsterdam : Elsevier
    Steroids 28 (1976), S. 467-480 
    Details
    ISSN: 0039-128X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0039-128X(76)90016-7
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  • 2
    Electronic Resource
    Electronic Resource
    The influence of age and multimorbidity on the pharmacokinetics and metabolism of spironolactone
    Amsterdam : Elsevier
    Archives of Gerontology and Geriatrics 3 (1984), S. 147-159 
    Details
    ISSN: 0167-4943
    Keywords: aging ; multimorbidity ; pharmacokinetics ; spironolactone
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-4943(84)90006-2
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  • 3
    Electronic Resource
    Electronic Resource
    Metabolism of Digoxigenin, digoxigeninmonodigitoxoside and digoxigeninbisdigitoxoside in rats (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 157-166 
    Details
    ISSN: 1432-1912
    Keywords: Digoxigenin-Digitoxosides ; 3-Ketodigoxigenin ; 3-Epidigoxigenin ; Conjugates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biliary and renal excretion products after i.d. administration of 3H-digoxigenin, 3H-digoxigenin-mono-digitoxoside and 3H-digoxigenin-bis-digitoxoside were studied in biliary fistula rats 65% and 58% of the given dose were excreted in bile and 10% and 5% in urine within 12 h after administration of mono-and-bis-glycoside respectively. Within 8 h, 45% and 4% of the given dose was eliminated in bile and urine after administration of digoxigenin. 93–95% of the excreted radioactivity consisted of CHCl3-soluble substances after administration of the bisglycoside, whereas the CHCl3-soluble fraction accounted for only 30–45% of the biliary eliminated radioactivity after administration of the monoglycoside and the genin. The main excretion product after administration of bis-digitoxoside was the unchanged bisglycoside. After administration of monodigitoxoside, digitoxoside, the CHCl3-soluble fraction in bile and urine was mainly represented by the monoglycoside and the 3-epigenin. Only traces of 3-ketogenin and no digoxigenin at all were detectable. The only CHCl3-soluble excretion product in bile after administration of digoxigenin was its epimer, while in urine a few per cent of unchanged digoxigenin and 3-ketogenin could be identified. The CHCl3-insoluble fraction after administration of bis- and-monodigitoxoside consisted of conjugation products with glucuronic and sulfuric acid. The monoglycoside was identified as the main conjugation partner after encymatic splitting of the polar fraction with β-glucuronidase and sulfatase. Therefore the hydroxyl in C3 of the steroid moiety cannot be conjugated preferentially with glucuronic or sulfuric acid during the metabolic decomposition of glycosides. This finding led to a degradation scheme of digoxin already discussed. Due to rapid metabolic inactivation of the monoglycoside to polar metabolites a therapeutic significance of this substance is very unlikely.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501188
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  • 4
    Electronic Resource
    Electronic Resource
    Quantitative analysis of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin and their metabolites in bile and urine of rats (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 273 (1972), S. 154-167 
    Details
    ISSN: 1432-1912
    Keywords: Digoxin and Derivatives ; Bis- and Monodigitoxosides ; Biliary Excretion ; Renal Excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolism of digoxin (D), 4‴-acetyldigoxin (AD) and 4″-methyldigoxin (MD) was studied in biliary fistula rats by quantitative analysis of the excretion of these glycosides after intraduodenal administration. The total activity excreted within 12 h in bile amounts to 45.1; 40.5; 21.3 and in urine to 11.6; 14.3; 17.6% of the dose of D, AD and MD respectively. AD undergoes a rapid, but incomplete desacetylation in the organism. The highest desacetylation activities were found in liver, in intestinal mucosa and in kidney. Yet considerable amounts of unchanged AD were found in portal vein blood and still another 1–2% of the dose in bile and urine. In contrast MD is very slowly demethylated. 15 min after intraduodenal administration portal vein blood contains almost exclusively MD. A stepwise cleavage of digitoxoses from D as well as of AD and MD is indicated. The absolute amounts of digoxigenin-bis-digitoxoside (4–8% of the dose), digoxigenin-mono-digitoxoside (2.5–8.5%) excreted in bile and urine were in the same range for all three glycosides examined, although the relative amounts of these metabolites in bile and urine were much higher after administration of MD than of the two other glycosides. In addition a water-soluble fraction could be detected in bile and urine after administration of D, AD and MD. The absolute quantities of polar metabolites (4.5–7.0%) excreted in bile and urine were identical for all three glycosides.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508087
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  • 5
    Electronic Resource
    Electronic Resource
    Kinetik der Elimination von 2-Propanol und seines Metaboliten Aceton bei Hund und Ratte (1969)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 264 (1969), S. 110-118 
    Details
    ISSN: 1432-1912
    Keywords: 2-Propanol ; Acetone ; Elimination ; Bateman-Function ; Schlüsselwörter ; 2-Propanol ; Aceton ; Elimination ; Bateman-Funktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Eliminationskinetik von 2-Propanol und dessen Metaboliten Aceton wird in Versuchen an Hund und Ratte nach Gabe von 1,0 g/kg 2-Propanol i.v. bzw. i.p. festgelegt. Die Elimination von 2-Propanol und Aceton folgt einem einfachen Exponentialgesetz. Der Acetonplasmaspiegel in der Zeit nach 2-Propanolgabe kann durch die Bateman-Funktion mit hinreichender Genauigkeit beschrieben werden. Ein Vergleich mit der Eliminationscharakteristik von Methanol und Äthanol zeigt, daß jeder dieser drei Alkohole bei seiner Elimination einer anderen Kinetik folgt.
    Notes: Summary The kinetics of elimination of 2-propanol and its metabolite acetone were determined in experiments on dogs and rats after administration of 1,0 g/kg 2-propanol i.v. and i.p. respectively. 2-propanol and acetone are eliminated according to a simple exponential function. The concentration of acetone in plasma following administration of 2-propanol can be described satisfactorily by the Bateman-function. Comparing the characteristics of elimination of methanol and ethanol to those of 2-propanol it becomes evident that each of these alcohols follows a different pattern in its elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997321
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  • 6
    Electronic Resource
    Electronic Resource
    Zum Mechanismus der 2-Propanoloxydation (1970)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 265 (1970), S. 411-424 
    Details
    ISSN: 1432-1912
    Keywords: Mechanism of 2-Propanol Oxidation ; Oxidation by ADH ; Influence of 1- and 2-Propanol on Ethanol Elimination ; Mechanismus der 2-Propanoloxydation ; Umsatz durch ADH ; Einflu\ von 1- und 2-Propanol auf die Äthanolelimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The elimination of 2-propanol from the blood of rats as well as from the isolated perfused rat liver is inhibited by ethanol and 1-propanol, whereas methanol and tert. butanol have no effect on the elimination of 2-propanol. Vice versa, 2-propanol delays ethanol elimination. 2-propanol has no influence on the elimination of 1-propanol in the concentration range examined. The results show that 2-propanol is metabolized by ADH. The change in the kinetics of the elimination of ethanol caused by 2-propanol and 1-propanol from zero to first and higher orders demonstrates a competition for ADH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997077
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  • 7
    Electronic Resource
    Electronic Resource
    A method for investigation of enterohepatic circulation (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 274 (1972), S. 208-210 
    Details
    ISSN: 1432-1912
    Keywords: Bile Flow ; Enterohepatic Circulation ; Operation Technics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method is described for simultaneous determination of a drug and its metabolites in blood and bile of rats with intact enterohepatic circulation. The comparison with the respective data obtained in biliary fistula animals allows a statement on enterohepatic circulation of the drug, if the bile flow is identical in both groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501857
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  • 8
    Electronic Resource
    Electronic Resource
    Evaluation of the enterohepatic circulation after 3H-digoxin administration in the rat (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 1-10 
    Details
    ISSN: 1432-1912
    Keywords: Enterohepatic Circulation ; Pharmacokinetics ; Digoxigenin-Bis- and Mono-Digitoxoside ; Polar Conjugates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After intraduodenal administration of 3H-digoxin (d) in biliary fistula (b.f.) rats, the total radioactivity in blood and bile is eliminated with t1/2 of 7 h in both fluids. In rats with intact enterohepatic circulation (e.c.), a t1/2 of 13.5 h was observed in blood and of 22 h in bile. To explain the much longer t1/2 in bile than in blood, the pharmacokinetics were studied of all substances, which might participate in e.c. after d administration. E.c. of the water soluble fraction is negligible since almost no absorption was found. Digoxigenin-bis- (b) and monodigitoxoside (m) showed approximately the same absorption kinetics as d. However, the blood levels of radioactivity after i.d. administration of these metabolites in b.f. rats were 5–6 times lower than those after d as a consequence of higher biliary excretion. 90–95% of the absorbed amounts of b and m were extrected in bile within 11 h compared with 61% after d administration. Thus the far longer t1/2 of elimination of radioactivity in bile than in blood after i.d. administration of d in rats with e.c. seemed to be due to a short circuit of b and m between intestine and liver. Evidence for this comes from the chromatographic analysis of the total radioactivity in the bile of these animals which shows that significantly more b is present in the bile of rats with e.c. than b.f. rats. No differences were found in the case of m, which on one hand is formed to a lesser extent and is on the other rapidly converted to polar metabolites, which are not reabsorbed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505063
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  • 9
    Electronic Resource
    Electronic Resource
    Distribution of digoxin, digitoxin and ouabain between plasma and erythrocytes in various species (1971)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 270 (1971), S. 105-116 
    Details
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Distribution in Blood ; Binding to Hemo-globin ; Binding to Erythrocyte Membranes ; Protein Binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of digoxin, digitoxin and ouabain between plasma and erythrocytes in the blood of different species was investigated. In man, cattle, dog, guinea-pig, cat and rat the ratios between erythrocytes and plasma were 0.90, 0.86, 0.90, 0.97, 2.32, 3.50 respectively for digoxin, 0.09, 0.19, 0.11, 0.21, 0.31, 0.26 respectively for digitoxin, and 0.03, 0.09, 0.01, 0.09, 0.09, 0.04 respectively for ouabain. When buffer solution was used instead of plasma these ratios changed only for digitoxin. The values for human, bovine and rat erythrocytes were 1.37, 1.25 and 2.87 respectively. These changes are most likely to be due to the strong binding of digitoxin to the plasma proteins. The percentage of unbound digitoxin in the plasma was 6.1 in man, 13.1 in cattle and 7.5 in rats. The greater uptake of digoxin by rat erythrocytes depended mainly upon its high affinity for rat hemoglobin and also on its attachment to membrane constituents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997082
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  • 10
    Electronic Resource
    Electronic Resource
    Conversion of spironolactone to canrenone and disposition kinetics of spironolactone and canrenoate-potassium in rats (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 283 (1974), S. 303-318 
    Details
    ISSN: 1432-1912
    Keywords: Spironolactone and Canrenoate-K ; Pharmacokinetics and Metabolism in Rats ; Biliary cycling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic conversion of spironolactone (I) to canrenone (II) was investigated using a chemical model reaction by treatment of spironolactone in aqueous medium at pH 13. The dethioacetylation proceeds in two steps, i.e., a fast hydrolysis to the 7α-thiol function present in congeners VI and VI0 (K 1=0.42 min−1), and a rate limiting step by elimination of H2S yielding the 4,6-dien-3-one function present in canrenone (II) and canrenoate (III) (K 2=0.13 h−1). The metabolic conversion of I to II was evaluated by intravenously injecting equimolar amounts of I, the 7α-thiol VI, II and III. Following injection of I, the only fluorigenic metabolites detectable were II, III, and an intermediate polar metabolite, which was identified by tlc and mass spectrometry as the 7α-thiol-17β-hydroxycarboxylic acid VI0. The plasma t 1/2 of I was 4 and 5 min, respectively, in two rats. The t 1/2 of VI0 amounted to 8 and 12 min, respectively, and roughly corresponded to the formation rate canrenone (II). Injection of the 7α-thiol VI resulted in plasma concentrations of VI0, II and III similar to those obtained from injection of I. It can be concluded that hydrolysis of the 7α-thioacetyl I to the 7α-thiol VI is a very rapid metabolic step, that the γ-lactone ring is in a rapid enzymatic equilibrium with the corresponding γ-hydroxylic acids, and that elimination of H2S from VI yielding II is the overall rate limiting step in the metabolic conversion of I to II. The elimination of intravenous doses of 3H-I and 3H-III occurred predominantly by biliary excretion of polar conjugated metabolites (80 and 95%, respectively, of the dose over 12 h) followed by extensive enterohepatic cycling. Urinary excretion remained below 3% of the dose over 12 h in bile fistula rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499190
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