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  • digoxin  (4)
  • drug interaction  (2)
  • plasma level  (2)
  • Sepsis  (1)
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  • 1
    ISSN: 1432-1238
    Schlagwort(e): Theophylline ; Ethylenediamine ; Pharmacokinetics ; Sepsis ; Multiorgan failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The pharmacokinetics of theophylline and ethylenediamine were examined in 6 patients with septicaemia and multiorgan failure (MOF). The patients received a bolus injection of 4mg/kg aminophylline. Aminophylline is the ethylenediamine salt of theophylline. The clearance of theophylline was reduced in all our patients ranging from 10–66% of the value obtained in healthy volunteers. The median t1/2β was 18.8h (range 5.8–25.5) compared to a normal value of 6h. The median clearance of ethylenediamine was 54% of the normal value, while the peripheral volume of distribution was increased to 650%. Due to this t1/2β was 2.3 (2.0–2.7)h, which is 5 times the normal value of 0.55h. There was no correlation between clearance of theophylline and ethylenediamine. As theophylline has a narrow therapeutic range, routine monitoring with measurements of serum theophylline is mandatory in patients with MOF.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1987), S. 447-453 
    ISSN: 1432-1041
    Schlagwort(e): atrial fibrillation ; verapamil ; slow-release formulation ; Holter monitoring ; multiple drug intake ; plasma level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twenty-four-hour heart rate control by verapamil given as conventional tablets t.d.s., or as a new slow release formulation once daily, has been compared in an open cross-over trial. Eight patients with chronic atrial fibrillation and one with chronic atrial flutter were studied outside hospital. Trough serum concentration of verapamil did not differ during the two dosage regimens (59 ng/ml — conventional formulation and 49.3 ng/ml — slow release tablet). The average serum concentration of digoxin in the patients was not changed. Compared to the control phase, both dosage regimens significantly and equally reduced individual and average heart rates throughout the entire 24-h period. A positive correlation between the serum concentration of verapamil and the relative increase in average R-R interval was demonstrated. It is concluded that dosage t.d.s. with conventional tablets of verapamil or once daily with the slow release formulation gave the same antiarrhythmic efficacy over 24 h, and was associated with equal trough serum concentrations of verapamil.
    Materialart: Digitale Medien
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  • 3
    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
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  • 4
    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
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 199-206 
    ISSN: 1432-1041
    Schlagwort(e): verapamil ; digoxin ; drug interaction ; digoxin pharmacokinetics ; inotropic effect ; systolic time intervals
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Verapamil has been demonstrated to inhibit the elimination of digoxin and to increase its steady state plasma level by 60–80%. Animal studies suggest that verapamil abolishes the intropic action of other drugs such as ouabain and dopamine. The clinical consequences of this drug interaction were investigated by examining the inotropic activity of single doses of digoxin (assessed from systolic time intervals), with and without coadministration of verapamil. Verapamil decreased total-body clearance of digoxin from 4.68±0.41 to 3.29±0.26 ml/min/kg (p〈0.001) and increased the plasma half-life of the drug from 33.50±2.38 to 41.31±2.27 h (p〈0.01). Verapamil had no influence on the base-line values of the systolic time intervals. Both in the absence and presence of verapamil, digoxin caused significant shortening of the total electromechanical systole and the left ventricular ejection time. However, compared to control conditions, the decay of these changes was slower in the presence of verapamil, in parallel with the prolongation of the plasma half-life of digoxin. A linear relationship was established between reductions in the systolic time intervals and the computer-derived concentration of digoxin in the deep compartment. These regression lines, which represent the concentration-effect relationships of the inotropism of digoxin, were not affected by verapamil. Thus, verapamil per se had no measurable effect either on base-line contractile function of the heart or on digoxin-induced inotropism. The elevated plasma digoxin concentration induced by verapamil appears cardioactive in terms of inotropism.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; verapamil ; digoxin-verapamil interaction ; kinetics ; plasma level ; renal clearance ; extra-renal clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Single-dose investigations in healthy subjects have demonstrated substantial impairment of renal and extrarenal clearance of digoxin during coadministration of verapamil. A longitudinal study has been performed to assess the changes in digoxin disposition during long-term verapamil therapy. After one week of verapamil 240 mg/d mean plasma digoxin had risen from 0.21±0.01 ng/ml (SE) to 0.34±0.01 ng/ml (p〈0.01), and renal digoxin clearance had fallen from 197.57±17.37 ml/min to 128.20±10.33 ml/min (p〈0.001). These changes gradually subsided, and after six weeks, renal digoxin clearance had normalized and plasma digoxin had declined to 0.27±0.02 ng/ml (NS). The 24-h urinary recovery of digoxin increased from 46.46±3.23% before to 69.78±3.69% (p〈0.001) after six weeks of verapamil co-administration, and this elevation persisted throughout the study. The verapamil-induced suppression of renal digoxin elimination disappears over a few weeks of drug exposure, whereas the inhibition of the extrarenal clearance of digoxin seems to persist.
    Materialart: Digitale Medien
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