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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 55 (1977), S. 641-646 
    ISSN: 1432-1440
    Keywords: α-Acetyldigoxin ; β-Acetyldigoxin ; Isomerisation ; Bioavailability ; In vivo Method ; In vitro Method ; α-Acetyldigoxin ; β-Acetyldigoxin ; Isomerisierung ; Biologische Verfügbarkeit ; In vivo Methode ; In vitro Methode
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An gesunden Versuchspersonen wurde die biologische Verfügbarkeit der Acetylester des Digoxins nach einmaliger wie nach mehrfacher Applikation bestimmt. Die relative Verfügbarkeit von α-Acetyldigoxin (Dioxanin®) ist um 30% geringer als die von β-Acetyldigoxin (Novodigal®). Auch eine Inkorporation von α-Acetyldigoxin in eine Aerosilmatrix als Trägersubstanz bewirkt keine signifikante Veränderung der biologischen Verfügbarkeit gegenüber dem β-Acetyldigoxin. In alkalischem Medium wird die Acetylgruppe aus der β-Position in die α-Position verlagert. Diese Isomerisierung führt zu einer Abnahme der biologischen Verfügbarkeit bei solchen Kombinationspräparaten, die β-Acetyldigoxin und hygroskopische Salze des Kalium-Magnesium-Aspartats (z.B. Gladixol®) enthalten. Nach Abisolierung des β-Acetyldigoxinanteils vom Kalium-Magnesium-Aspartat in der Tablette wird eine dem Monopräparat (Novodigal®) vergleichbare biologische Verfügbarkeit erreicht und damit auch eine gleiche therapeutische Äquivalenz. Die Untersuchungen zeigen, daß die biologische Verfügbarkeit entscheidend von den physiko-chemischen Eigenschaften des Wirkstoffes und seiner galenischen Zubereitung beeinflußt werden kann.
    Notes: Summary Bioavailability of acetylated derivatives of digoxin tablets have been studied in healthy subjects after a single oral and intravenous dose as well as during maintenance therapy. α-acetyldigoxin shows a lower bioavailability than β-acetyldigoxin even if the α-acetylated derivative is incorporated in a matrix of aerosil (SiO2). Moreover, β-acetyldigoxin can be transferred to α-acetyldigoxin in alkaline solutions. This isomerisation leads to a decrease of the bioavailability of such fixed preparations which contain β-acetyldigoxin and the hygroscopic salts of potassium-magnesium-aspartate. A prevention of the isomerisation is attained by isolating β-acetyldigoxin from potassium-magnesium-aspartate. The bioavailability of a such new formulation is comparable to that of β-acetyldigoxin alone. The experiments show the bioavailability of acetylated derivatives of digoxin to be influenced by the physico-chemical properties of a drug and its preparation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 55 (1977), S. 429-438 
    ISSN: 1432-1440
    Keywords: Digoxin ; Urine ; Digoxin Antibody Complex ; Variation ; Bioavailability ; Digoxin ; Urin ; Digoxin-Antikörperkomplex ; Streuung ; Verfügbarkeit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Dextran-Aktivkohlesuspensionen entwickeln in proteinfreien Urinverdünnungen verbessert Siebeffert in der Trennung von freiem und an Antikörper gebundenem Digoxin, der sich mit zunehmender Alterung der Suspension verbessert. Zusatz von Albumin zum Verdünnungsmedium (Puffer) stabilisiert die Adsorptionseigenschaften. Bei Urinverdünnungen von 〈1:50 werden falsch positive Digoxinkonzentrationen gemessen. Bestimmungen von 0–5 ng Digoxin/ml im verdünnten Urin (1:100) und in der Pufferlösung ergeben identische Werte. Die Wiederfindungsrate von zugesetztem Digoxin (1 ng und 2 ng/ml) beträgt 100%; die untere Nachweisgrenze 3,6 µg/l Urin. Mittelwerte von Doppelbestimmungen verschiedener Analysengänge weisen für den Hauptmeßbereich (1,5–2.8 ng Digoxin/ml) einen Variationskoeffizienten von 〈4.5% auf; dieser Wert ist für einen kommerziellen Test mehrfach höher bestimmt worden. Dihydrodigoxin wird nur zu 3% erfaßt. Die Anwendung der Methode zur Erfassung der kumulativen Glykosidausscheidung im Urin bei 5 Versuchspersonen (0,5 mg Digoxin täglich i.v. über 14 Tage) ergibt eine minimale interindividuelle Streuung von 5.1%. Bei einem Versuchspräparat, welches eine biologische Verfügbarkeit von 94,6% ergeben hat, beträgt die Streuung 5,2%.
    Notes: Summary When separating free and antibody bound digoxin, dextrancoated charcoal suspensions in protein-free urine dilutions develop an improves sieve effect which improves with aging of the suspensions. On addition of albumin to the dilution medium (buffer), the adsorptive capacities become stabilized. In urine dilutions 〈 of 1:50, false positive digoxin concentrations were measured. Determinations of 0–5 ng digoxin/ml in the diluted urine (1:100) and in the buffer solution show identical results. The recovery of added digoxin (1 ng and 2 ng/ml) is 100%; the lower detection limit is 3.6 µg/l urine. Betweenassay variation for means of duplicates shows in the main measuring range (1.5–2.8 ng digoxin/ml) a variation coefficient 〈 of 4.5%; for a commercial test this value is distinctly higher. Dihydrodigoxin is measured at 3% only. Application of this method for measuring cumulative glycoside elimination of 5 healthy persons (0.5 mg digoxin daily intravenously during 2 weeks) results in a minimal interindividual variation of 5.1%. In a test preparation with a bioavailability of 94.6% the variation is 5.2%.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 387-392 
    ISSN: 1432-1041
    Keywords: Digoxin ; β-methyldigoxin ; prolonged administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers received digoxin 0.4 mg or β-methyldigoxin 0.4 mg i. v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and β-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54±0.31 days was significantly shorter than the half life of 2.29±0.34 days for β-methyldigoxin. The distribution volume of 807±187 liters for digoxin was not significantly larger than the 735±227 liters for β-methyldigoxin. Renal digoxin clearance of 191±25 ml/min was significantly higher than both the renal clearance of β-methyldigoxin of 111±23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of β-methyldigoxin injected once a day, which was significantly higher than the 1.8-fold accumulation of digoxin.
    Type of Medium: Electronic Resource
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