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PubMed1989

Digoxin-like substance in the serum of uremic patients before and after hemodialysis.

Digoxin concentrations in serum samples were measured before and after hemodialysis of 31 uremic patients (pts) who either never took digoxin or who had not taken digoxin for at least 1 year. False positive digoxin was found in 22 of 31 patients (71%) before hemodialysis and in 14 of 31 patients (45%) after hemodialysis. The concentrations ranged from 0.1 to 0.5 nmol/L, mean value was 0.20 +/- 0.16 before hemodialysis and after hemodialysis ranged 0.1 to 0.4 nmol/L mean value was 0.11 +/- 0.14 nmol/L. The difference before and after hemodialysis is statistically significant. Some of the patients had a constant value before and after hemodialysis. None had a higher value after hemodialysis than they did before. Eight patients, who had positive serum digoxin before hemodialysis with concentrations up to 0.5 nmol/L, became negative after hemodialysis. Our results indicate that a digoxinlike substance in uremic serum could be at least partly dialyzable.

Adolescent↗
PubMed1990

Oral salbutamol decreases serum digoxin concentration.

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.l-1). It also reduced the serum potassium concentration (0.58 mmol.l-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.

Adult↗
PubMed1983

Possible mechanism of digoxin-induced convulsions.

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.

Animals↗
PubMed1978

Postmortem tissue and plasma concentrations of digoxin in newborns and infants.

Postmortem tissue and plasma concentrations of digoxin were studied in 13 premature newborns, 6 mature newborns, and 5 older infants (age 1 to 14 months). The pertinent results of our study are as follows: The tissue digoxin concentrations tend to be higher in premature and mature newborns than in infants. This difference is statisitcally significant with respect to the concentration in myocardium and skeletal muscle. The renal digoxin concentration of premature newborns is significantly lower than that of mature newborns, the tissue concentrations in the other organs examined being essentially equal. In all age groups examined, skeletal muscle contains the greatest portion of digoxin, followed by the liver. The relation of myocardial to plasma digoxin concentration shows no significant difference between the various age groups. Within the groups, the variation is relatively large.

Autopsy↗
PubMed1977

Digoxin elimination by exchange transfusion.

The report covers four cases presenting simultaneous indications for digitalisation and exchange transfusions. Intravenous administration of digoxin was followed: 1. by monitoring of the behaviour of the plasma digoxin level; 2. by determination of the total amount of glycoside eliminated by the blood exchange. Particular attention was paid to the effect of the delay between injection and exchange transfusion on the amount of digoxin eliminated. All four cases showed moderate falls in plasma levels. The amounts of digoxin eliminated by exchange transfusion were in reverse relationship to the delay between administration of digoxin and the blood exchange. At no time did the eliminated fraction exceed 5% of the total amount present in the body.

Child, Preschool↗
PubMed1976

Effects of acetylcholine and atropine on the bile flow and biliary excretion of digoxin in the isolated perfused rat liver.

The effects of acetylcholine (ACh). physostigmine, and atropine on bile flow and biliary elimination of digoxin were investigated using isolated rat liver perfusion. 1. ACh in the presence of physostigmine caused a temporary reduction in the bile secretion, while physostigmine alone had no effect on the bile flow. 2. The biliary concentration of radioactivity derived from 3H-digoxin was slightly decreased after an addition of physostigmine alone. This effect of physostigmine was not potentiated by ACh. 3. The addition of ACh decreased transiently the biliary elimination of digoxin, as a result of the reduced bile flow. 4. Atropine in the concentration range of 10(-6)-10(-5) M in the perfusion medium did not affect bile flow or biliary excretion of digoxin; repeated addition of atropine (2 X 2 X 10(-4) M) caused a choleresis lasting over the perfusion period. 5. This choleresis induced by atropine was associated with decreased concentration of tritium in the bile but slightly increased biliary elimination of total radioactivity. 6. The results allow us to draw the conclusion that ACh in the presence of physostigmine has an inhibitory action on bile flow and biliary elimination of digoxin in the isolated perfused rat liver.

Acetylcholine↗
PubMed1989

Effect of salbutamol on digoxin concentration in serum and skeletal muscle.

Beta 2-receptor stimulation has been reported to increase the concentration of 3H-ouabain in rat skeletal muscle. The present study was undertaken to see if beta 2-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 micrograms.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.

Adult↗
PubMed1989

Interaction study of fenoldopam--digoxin in congestive heart failure.

The potential interaction between fenoldopam, a DA1 selective agonist, and digoxin has been studied in 10 patients with heart failure (NYHA Class II or III) on chronic digoxin treatment. Plasma levels and urinary recovery of the glycoside were monitored for 24 h before and after 9 days of treatment with fenoldopam 100 mg tid. Fenoldopam caused a small, non-significant decrease in the mean steady state plasma concentration and area under the plasma concentration curve of digoxin. As the clearance of digoxin was unchanged there does not appear to be an interaction between fenoldopam and digoxin at the level of the renal tubule.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1981

Digoxin-associated thrombocytopaenia.

A 60-year-old male patient had two episodes of thrombocytopaenia whilst being treated with digoxin, each of them reversible upon withdrawal of the drug. Bone marrow examination was consistent with peripheral platelet destruction as the main mechanism of the thrombocytopaenia. The inhibition of clot retraction test was positive, with a declining titer, after cessation of digoxin therapy, and this plus the finding of circulating immune complexes after incubation of the patient's serum with digoxin established digoxin as the offending agent. It is concluded that digoxin may be a rare cause of drug-induced immune-thrombocytopaenia.

Digoxin↗
PubMed1980

Absorption of digoxin from a new microencapsulated formulation.

The absorption of digoxin from two capsule preparations containing a large number of small, enteric-coated granules of the glycoside (0.38 mg) was compared with that of the same amount from ultrarapidly dissolving commercial tablets. Eight volunteers were studied during steady state conditions. Digoxin concentrations in plasma and urine were measured by radioimmunoassay. Peak plasma concentrations of digoxin were significantly (p < 0.01) delayed after taking the capsules (2.6 +/- 1 h and 2.6 +/- 0.9 h, mean +/- SD) as compared to the tablets (1.3 +/- 0.7 h). The peak concentrations produced by the capsules were 3.1 +/- 1.0 and 2.6 +/- 1.1 nmol/l; only the latter was significantly (p less than 0.05) lower than after the tablets (3.4 +/- 1.0 nmol/l). Areas under the plasma concentration-time curves during a 24 h dosage interval were similar for the three preparations, and so was the 24 h urinary excretion of digoxin, which averaged 60-63% of the daily dose. Thus, this particular enteric coating of digoxin delayed absorption without reducing the amount absorbed.

Adult↗
PubMed1987

Skeletal muscle binding and renal excretion of digoxin in man.

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.

Adult↗
PubMed1987

Verapamil-induced changes in digoxin kinetics in cirrhosis.

The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.

Adult↗
PubMed1976

Serum digoxin levels in patients of a general practice in Germany.

Serum digoxin levels were determined in 33 outpatients of a general practice in the countryside, on three occasions at intervals of 8 weeks. All the patients were on long term digoxin treatment, about 2 years on average. About 14 days after the first and the second visits the results of the measurements were sent to the patients, with a comment about their reliability in taking treatment according to the serum digoxin level. At the first visit half of the serum digoxin level were lower than 0.5 ng/ml; the mean serum concentration was 0.52 ng/ml. There was no correlation between serum concentration and age, dose or creatinine level; but there was with replies to the question about regularity of drug intake. The mean serum level at the second and the third visits was 0.88 ng/ml and 0.89 ng/ml, respectively. A correlation was found between the dose and the serum digoxin level. From these results it seems that compliance by the patient plays a major role in producing steady state levels of drugs.

Aged↗
PubMed1975

Absorption of digoxin in infants.

The bioavailability of digoxin in solution was studied in 4 newbron infants with heart failure. Serum digoxin concentrations were determined by radioimmunoassay using 125I. Bioavailability was estimated by camparison of the areas under the 8-h serum concentration curves (8-h AUC) after intravenous and oral administration of the glycoside. After oral administration of digoxin (1/4 of the digitalizing dose, 0.05 mg/kg bw), peak serum values of 2.3-4.4 ng/ml were reached within 30-90 min. After intravenous administration of the same amount of the glycoside, there was a rapid decrease in serum concentration during the first 2 h, and after about 4 h the serum concentration curves paralled those obtained after oral dosing. Based on within subject comparison of intravenous and oral 8-h AUC'S, the mean bioavailability of digoxin was estimated to be 72 per cent (range 52-79 per cent). It was concluded that digoxin in solution, given to infants with mild to moderate heart failure, is well absorbed and biologically available to the same extent as in adults.

Administration, Oral↗
PubMed1980

Digoxin concentration in right atrial myocardium, skeletal muscle and serum in man: influence of atrial rhythm.

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, 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).

Adult↗
PubMed1981

Evidence of nonlinearity in digoxin pharmacokinetics.

Six normal male volunteers received 0.5 mg label doses of digoxin as (a) a bolus intravenous injection over 2 min, (b) a constant rate intravenous infusion over 1 hr, (c) a constant rate intravenous infusion over 3 h, and (d) a solution in 5% dextrose given orally. Plasma concentrations of digoxin were measured by radioimmunoassay for a 4 day period and urinary excretion for a 6 day period after the single doses. The mean (coefficient of variation) total areas under the plasma concentration-time curves per 0.5 mg of digoxin were (a) 35.55 (14.8%), (b) 30.20 (27.7%), (c) 25.80 (35.5%), and (d) 15.47 (49.9%); the means differed significantly (0.01 greater than p greater than 0.005). The mean (coefficient of variation) total amounts excreted in the urine as a fraction of the dose were (a) 0.689 (6.31%), (b) 0.517 (20.4%), (c) 0.588 (16.8%), and (d) 0.374 (23.4%); the means differed significantly (p less than 0.001). Both the total clearance and the nonrenal clearance of digoxin differed significantly with the method of intravenous administration. The slower the rate of input of digoxin to the body, the greater were both the total clearance and the nonrenal clearance of the drug, which strongly suggests nonlinear pharmacokinetics.

Biological Availability↗
PubMed1978

[Plasma digoxin concentration in different age groups (author's transl)].

Plasma digoxin concentration during maintenance therapy with digoxin was determined in premature and mature newborns, infants, children and adults. The plasma digoxin concentration of newborns was significantly higher than in adults; in addition, in the group of premature newborns it also was higher than in infants and children. These differences in plasma digoxin concentrations may be explained by differences in dose, volume of distribution and excretion rate of digoxin in the various age groups.

Adolescent↗
PubMed1983

Influence of digoxin on sinus node function after pharmacologic autonomic blockade.

The effect of iv digoxin on normal sinus node function was studied after pharmacologic autonomic blockade (AB) in ten patients. Sinus cycle length (SCL), sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined before and after AB with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg body weight) iv, and 15 min, 30 min, and 45 min after 1 mg iv digoxin. AB resulted in a significant decrease (P less than 0.01) in SCL (916 +/- 158 to 716 +/- 120 ms), in SNRT (1,229 +/- 221 to 871 +/- 190 ms), and in SACT (79 +/- 34 to 44 +/- 10 ms). Fifteen minutes after iv digoxin there was no significant change observed in SCL (716 +/- 120 to 708 +/- 92 ms), in SNRT (871 +/- 190 to 864 +/- 148 ms), or in SACT (44 +/- 10 to 46 +/- 15 ms). Similar results were obtained 30 min after digoxin administration. It is concluded that a single therapeutic dose of digoxin has no direct effect on electrophysiologic parameters of normal intrinsic sinus node function.

Adult↗