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  • Artikel: DFG Deutsche Nationallizenzen  (2)
  • quinidine  (2)
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  • Artikel: DFG Deutsche Nationallizenzen  (2)
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 263-270 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; quinidine ; ouabain ; cell binding constants ; lymphocytes ; mononuclear cells ; drug interaction ; glycoside receptor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To explore the molecular basis of the glycoside-quinidine interaction, the in vitro effect of quinidine on the binding of [3H]-ouabain and [3H]-digoxin to Na+ K+ ATPase receptors on human mononuclear cells was investigated. The maximum [3H]-ouabain binding capacity was 45.7±9.4×103 molecules/cell in pure lymphocyte preparations (n=8) and 75.5±7.3×103 molecules/cell in mixtures of mononuclear cells (n=8). These parameters were not influenced by 10−5 M quinidine. In eight equilibrium experiments with pure lymphocytes, the dissociation constant of [3H]-ouabain increased from 0.79±0.26×10−8 M in the absence of 10−5 M quinidine to 1.56±0.74×10−8 M in its presence (p〈0.01), indicating that the affinity of the drug was decreased. Similar findings were observed using mixed mononuclear cells. In five uptake and release experiments, quinidine decreased the association rate constant of [3H]-ouabain from 3.15±0.36×104 M−1×s−1 to 2.01±0.37×104 M−1 s−1 (p〈0.01), whereas the dissociation rate constant was not affected. A therapeutic concentration of quinidine does not affect the number of glycoside receptors on lymphocytes, but it does appear to reduce fractional receptor occupancy by both [3H]-ouabain and [3H]-digoxin at lower tracer concentrations. This finding is compatible with the clinical observation that quinidine reduces the distribution volume of digoxin.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 41-47 
    ISSN: 1432-1041
    Schlagwort(e): quinidine ; digoxin ; interaction ; kinetics ; absorption ; elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate constant of digoxin (ka) increased from 2.72±1.04 to 3.53±1.34 h−1 (p〈0.05), whereas lag time and peak time decreased from 0.16±0.10 to 0.05±0.04 h (p〈0.05) and from 0.92±0.27 to 0.69±0.19 h (p〈0.02), respectively. Predose plasma digoxin increased from 0.41±0.25 to 0.70±0.31 ng/ml (p〈0.02), while peak plasma digoxin increased from 0.93±0.34 to 1.63±0.46 ng/ml (p〈0.02). The systemic availability of digoxin increased from 68.48±13.35 to 79.09±14.89% (p〈0.05) in the presence of quinidine. Quinidine had no effect on the biotransformation pattern of digoxin, as assessed by thin layer chromatography. Quinidine increases the rate and extent of digoxin absorption, and this interaction contributes significantly to the elevation in plasma digoxin during both its distribution and elimination phases.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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