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  • 11
    Electronic Resource
    Electronic Resource
    Effect of salbutamol on digoxin pharmacokinetics (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 197-201 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278484
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  • 12
    Electronic Resource
    Electronic Resource
    Digoxin concentration in right atrial myocardium, skeletal muscle and serum in man: Influence of atrial rhythm (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 243-250 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; atrial fibrillation ; digoxin concentrations in right atrium ; skeletal muscle ; serum ; sinus rhythm ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum, right atrial myocardium and skeletal muscle collected from 32 adult patients undergoing open heart surgery were analyzed for digoxin by radioimmunoassay. Preoperatively 20 patients were in sinus rhythm and 12 were in atrial fibrillation. In patients with sinus rhythm, but not in patients with atrial fibrillation, there was a highly significant correlation between digoxin concentration in serum and right atrial myocardium, in skeletal muscle and right atrial myocardium, and in serum and skeletal muscle. The means and variances of the ratios right atrial myocardium/serum and right atrial myocardium/skeletal muscle were significantly higher in patients with atrial fibrillation than in those with sinus rhythm. This, plus the lack of difference in ratios skeletal muscle/serum between these groups of patients, indicate increased right atrial digoxin binding in atrial fibrillation in man. This conclusion is further supported by the finding of similar or higher digoxin concentration in right atrial myocardium than in left ventricular myocardium in atrial fibrillation (6 patients), and a lower digoxin concentration in right atrial myocardium than in left ventricular myocardium in sinus rhythm (3 patients).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00625797
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  • 13
    Electronic Resource
    Electronic Resource
    Skeletal muscle digoxin concentration and its relation to serum digoxin concentration and cardiac effect in healthy man (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 89-95 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; muscle biopsy ; skeletal muscle levels ; serum levels ; systolic time intervals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood samples and skeletal muscle biopsies (m. quadriceps femoris, vastus lateralis) were taken from seven healthy subjects for analysis of serum and skeletal muscle digoxin concentrations by radioimmunoassay using a percutaneous needle biopsy technique for muscle sampling. The subjects were investigated on two digoxin dose levels and on the third day after withdrawal of digoxin. It was found that the skeletal muscle/serum digoxin ratio was significantly higher than the corresponding ratio obtained in a previous study with muscle sampling (m. rectus abdominis) from patients during open heart surgery. The present study indicates a significant correlation between the digoxin concentrations in serum and skeletal muscle as well as between cardiac effect, measured by changes in QS2I, and skeletal muscle digoxin concentration. A doubling of the digoxin dose gave a proportional increase in skeletal muscle digoxin concentration. The magnitude of the estimated half-life of skeletal muscle digoxin was the same as previously reported for serum or plasma digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568394
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  • 14
    Electronic Resource
    Electronic Resource
    Skeletal muscle digoxin concentration during digitalization and during withdrawal of digoxin treatment (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 97-105 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; skeletal muscle levels ; serum levels ; slow digitalization ; half-time of elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood samples and skeletal muscle biopsies (m. quadriceps femoris, vastus lateralis) were taken from 15 patients during digitalization or during withdrawal of digoxin treatment for analysis of serum and skeletal muscle digoxin concentrations. A percutaneous needle biopsy technique was used for muscle sampling and digoxin was analysed by radio-immunoassay. During “slow” digitalization with 0.25 mg digoxin daily the skeletal muscle digoxin concentrations after 2 and 4 days were 45% (range 19%−62%; n=3) and 78% (range 56%−92%; n=3) respectively, of the steady state concentration (defined as the digoxin concentration after 25–40 days of treatment). After 9 and 11 days of treatment the skeletal muscle digoxin concentrations were 106% (range 84%–133%; n=5) and 116% (range 72%–164%; n=3) respectively, of the steady state concentration. A doubling of the digoxin dose gave a proportional increase in skeletal muscle digoxin concentration (three patients). The magnitude of the estimated half-life of skeletal muscle digoxin was the same as previously reported in healthy subjects. No significant correlations were found between changes in systolic time intervals and steady state serum or skeletal muscle digoxin concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568395
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  • 15
    Electronic Resource
    Electronic Resource
    Physical exercise and digoxin binding to skeletal muscle: Relation to exercise intensity (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 585-588 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; skeletal muscle exercise ; serum digoxin ; tissue binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a 1 h bicycle exercise test on digoxin concentration in skeletal muscle (thigh) and serum was studied in 10 healthy men, who had ingested digoxin 0.5 mg daily for 2 weeks. During maintenance digoxin treatment each subject performed 2 exercise tests, at 70–90 W and 140–180 W both 24 h after the last dose, at a 2–7 day interval. During exercise at the lower work load the mean skeletal muscle digoxin concentration increased by 9% (n.s.) and the mean serum digoxin concentration decreased by 26% (p〈0.001). The high work load induced a mean increase in skeletal muscle digoxin of 20% (p〈0.05) and a mean decrease in serum digoxin of 40% (p〈0.001). The results indicate that the increased uptake of digoxin into exercised skeletal muscle and the decrease in serum digoxin during exercise is related to the intensity of the exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542343
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  • 16
    Electronic Resource
    Electronic Resource
    Quinidine-induced changes in serum and skeletal muscle digoxin concentration; evidence of saturable binding of digoxin to skeletal muscle (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 571-575 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; digoxin ; drug interaction ; serum digoxin ; skeletal muscle digoxin ; tissue binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with atrial fibrillation on maintenance digoxin therapy were investigated by analysis of serum (SDC) and skeletal muscle (SMDC) digoxin concentrations before and 24 h and 2 weeks after starting quinidine treatment. After cardioversion the maintenance dose of digoxin was reduced in order to obtain the same steady-state SDC after 2 weeks, as before quinidine. SDC was increased by quinidine therapy from 1.56 to 2.40 nmol/1 after 24 h. With the reduced digoxin dose SDC was 1.68 nmol/1 after 2 weeks. The ratio SMDC/SDC decreased after 24 h of quinidine treatment from 35.4 to 29.0 (p〈0.01). After 2 weeks of quinidine treatment with the reduced digoxin dose, the ratio had risen to 38.1, which did not differ significantly from the initial ratio. The present data suggest that the reduced skeletal muscle binding of digoxin during quinidine therapy is due to saturation of digoxin binding sites secondary to the increase in the total body load of digoxin at steady-state, and not to direct interference by quinidine with digoxin binding sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556894
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  • 17
    Electronic Resource
    Electronic Resource
    Physical exercise and binding of digoxin to skeletal muscle — Effect of muscle activation frequency (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 567-570 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; tissue binding ; skeletal muscle exercise ; serum digoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy subjects who had ingested 0.5 mg digoxin daily for at least 10 days, performed a 1-hour bicycle exercise test on two occasions, 24 h after the latest dose, with the same work load but at two different pedalling rates, 40 and 80 rpm. During exercise the mean digoxin concentration in the thigh muscle increased by 8% at 40 rpm (n.s.) and by 29% at 80 rpm (p〈0.01). The serum digoxin concentration decreased by 39% at both pedalling rates (p〈0.001). The results suggest that the increase in skeletal muscle digoxin concentration during exercise is related to the neuromuscular activation frequency. The digoxin concentration in erythrocytes was measured in 16 healthy subjects before and 1 minute after a 1-hour bicycle exercise test. The erythrocyte digoxin concentration decreased by 12% (p〈0.01) during the exercise indicating that the increased uptake of digoxin in skeletal muscle during exercise influences the digoxin concentration in other tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00556893
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  • 18
    Electronic Resource
    Electronic Resource
    Effect of salbutamol on digoxin concentration in serum and skeletal muscle (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 235-238 
    Details
    ISSN: 1432-1041
    Keywords: salbutamol ; digoxin ; beta2-adrenoceptor stimulation ; serum-/skeletal muscle digoxin concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Beta2-receptor stimulation has been reported to increase the concentration of3H-ouabain in rat skeletal muscle. The present study was undertaken to see if beta2-adrenoceptor stimulation by i.v. injection of salbutamol had any influence on the pharmacokinetics of digoxin in man. Ten volunteers were digitalized with digoxin and were investigated on two occasions. On each occasion a muscle biopsy was taken from the quadriceps after 2 h of supine rest. An injection of salbutamol 4 µg·kg−1 b.wt. or saline was then given intravenously. Blood samples were taken before and after the injection and further muscle biopsy was taken from the same thigh 120 min after the injection. Compared to the injection of saline, salbutamol caused a decrease in the serum digoxin and potassium concentrations. The change in serum potassium was significantly correlated with that in digoxin. The digoxin concentration in skeletal muscle was not significantly changed by either the salbutamol or saline injections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558153
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  • 19
    Electronic Resource
    Electronic Resource
    Oral salbutamol decreases serum digoxin concentration (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 195-197 
    Details
    ISSN: 1432-1041
    Keywords: Salbutamol ; digoxin ; beta2-adrenoceptor stimulation ; serum digoxin ; skeletal muscle digoxin concentration ; drug interaction ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a therapeutic dose of oral salbutamol on serum and skeletal muscle digoxin concentrations has been studied in volunteers digitalised with digoxin. On one occasion a biopsy was taken from the quadriceps after 2 h of supine rest and then 3–4 mg salbutamol was given orally. Blood samples were taken before and after that dose and another muscle biopsy specimen was taken from the same thigh 180 min after the medication. On another occasion control blood sampling, ECG and blood pressure recordings were made but without muscle biopsies or salbutamol administration. Compared to the control measurements, salbutamol decreased the serum digoxin concentration (0.30 nmol·1−1). It also reduced the serum potassium concentration (0.58 mmol·1−1). The digoxin concentration in skeletal muscle did not change significantly after the intake of salbutamol. Thus, even a therapeutic oral dose of salbutamol reduces the serum digoxin concentration in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265984
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  • 20
    Electronic Resource
    Electronic Resource
    Skeletal muscle binding and renal excretion of digoxin in man (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 601-603 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; serum digoxin ; skeletal muscle binding ; renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten healthy subjects were treated with three or four different doses of digoxin, 0.25 to 0.88 mg daily, in random order. Digoxin concentrations in serum (SDC) and skeletal muscle (SMDC) were determined as well as its renal clearance after 2 weeks of treatment with each dose. The mean ratio SMDC/SDC decreased non-significantly by about 20% from 33±15 at the lowest SDC interval (0.5–0.9 nmol/l) to 28±7 at the highest concentration interval (2.0–2.4 nmol/l). This is in accordance with findings from previous studies. No significant change was observed in the renal clearance of digoxin with increasing digoxin concentration, supporting the concept of first-order renal elimination of digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606638
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