Search PubMed⌕ Search

Biomedical subjects

K E Pedersen

Publications and source records attributed to K E Pedersen.

At least 73 records · Page 4Linked to original sources
PubMed1983

The diagnostic value of determination of intraerythrocytic sodium and potassium concentrations versus plasma digoxin concentration in digoxin intoxication.

Plasma digoxin measurements have proved unserviceable as a means of differentiating between toxic and non-toxic patients. In order to assess the value of a biological effect of digoxin in this discrimination, intraerythrocytic sodium and potassium concentrations were determined in 55 chronically digitalized patients of whom 10 were digoxin-intoxicated according to ECG criteria. Digitoxicity was associated with elevated intraerythrocytic sodium concentration (mean +/- SEM 19.3 +/- 1.2 versus 11.3 +/- 0.3 mmol/l, p less than 0.001) and reduced intraerythrocytic potassium concentration (94.6 +/- 2.3 versus 100.0 +/- 0.6 mmol/l, p less than 0.001) compared to non-toxic patients. Mean (+/- SEM) plasma digoxin concentrations in the two groups were 3.14 +/- 0.41 and 1.57 +/- 0.09 nmol/l, respectively (p less than 0.001). When diagnosing toxicity in chronically digitalized patients, plasma digoxin and intraerythrocytic sodium determinations showed sensitivities of 60 and 100%, respectively. The predictive values of a positive test were 75% for plasma digoxin and 83% for intraerythrocytic sodium.

Aged↗
PubMed1983

The characteristics of [3H]-ouabain binding to human lymphocytes.

The kinetic characteristics of [3H]-ouabain binding to human lymphocytes and mixtures of mononucleated cells, and the maximum [3H]-ouabain binding capacities of these cells were studied. The [3H]-ouabain binding was compatible with a single class of receptors with a high affinity for the drug. No signs of positive or negative cooperativity could be demonstrated. In six experiments with pure lymphocyte preparations, the association and dissociation rate constants were 3.08 +/- 0.34 X 10(4)/M/S and 1.58 +/- 0.50 X 10(-4)/S. The dissociation constant derived from equilibrium studies on lymphocytes was 0.68 +/- 0.21 X 10(-8) M, which was identical to that of mononucleated cells. In healthy subjects the maximum [3H]-ouabain binding capacities, which reflect the number of sodium/potassium pump sites were 43154 +/- 8037 molecules/cell (n = 25) in lymphocytes and 75474 +/- 6764 (n = 9) molecules/cell in mixtures of mononucleated cells. Direct determination of the [3H]-ouabain binding capacity of lymphocytes can be performed with acceptable accuracy and precision using 30 ml whole blood. Provided high cell purity, this method may be useful, when studying sodium/potassium pump function in clinical settings.

Humans↗
PubMed1983

Changes in steady state digoxin pharmacokinetics during quinidine therapy in cardiac patients: influence of plasma quinidine concentration.

In seven cardiac patients on long-term digoxin therapy, digoxin kinetics were investigated - in the absence and presence of quinidine - after simultaneous administration of an oral digoxin dose and an intravenous 3H-digoxin bolus injection. From 3H-digoxin data quinidine was found to decrease both renal (from 1.19 +/- 0.35 to 0.86 +/- 0.21 ml/min./kg) (P less than 0.02) and extrarenal clearances of digoxin (from 0.85 +/- 0.24 to 0.49 +/- 0.23 ml/min./kg) (P less than 0.02), and to diminish the steady state distribution volume of the drug (from 6.78 +/- 1.23 to 5.63 +/- 1.64 l/kg) (P less than 0.02). Plasma half-life increased from 51.5 +/- 5.4 to 64.4 +/- 14.8 hrs (P less than 0.05), while urinary excretion half-life increased from 54.4 +/- 3.9 to 78.5 +/- 14.1 hrs (P less than 0.01). Pharmacokinetic parameters derived from plasma and urinary digoxin data showed similar changes during quinidine therapy. Reduction in renal 3H-digoxin clearance occurred at subtherapeutic plasma quinidine levels and was independent of plasma quinidine, whereas reductions in extrarenal 3H-digoxin clearance and 3H-digoxin distribution volume were positively correlated to plasma quinidine concentrations (P less than 0.05).

Creatinine↗
PubMed1982

The long-term effect of verapamil on plasma digoxin concentration and renal digoxin clearance in healthy subjects.

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 less than 0.01), and renal digoxin clearance had fallen from 197.57 +/- 17.37 ml/min to 128.20 +/- 10.33 ml/min (p less than 0.001). These changes gradually subsided, and after six weeks, renal digoxin clearance had normalized and plasma digoxin had declined to 0.27 +/0 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 less than 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.

Adult↗
PubMed1982

Effect of nifedipine on digoxin kinetics in healthy subjects.

Verapamil has been shown to reduce total-body digoxin clearance by 35% due to impairments of both renal and extrarenal clearances. Our study was undertaken to evaluate the influence of the related calcium antagonist nifedipine on single-dose kinetics. Nifedipine increased extrarenal clearance of digoxin from 1.09 +/- 0.30(SD) to 1.45 +/- 0.23 ml/min/kg (P less than 0.05) and reduced the total urinary recovery of the drug from 69.2% +/- 5.9(SD) to 64.3% +/- 5.2 (P less than 0.05). There were no significant changes in renal digoxin clearance, distribution, or biological half-life or in digoxin distribution volumes during nifedipine coadministration.

Adult↗
PubMed1982

Intraerythrocytic sodium and potassium concentrations during acute and chronic digitalization.

To assess the cellular effects of digoxin, intraerythrocytic sodium and potassium concentrations were measured in 17 patients during the early phase of digitalization, in 45 patients on long-term therapy and in 64 non-digitalized control patients. Acute digitalization raised intraerythrocytic sodium from 11.6 +/- 0.4 to 16.7 +/- 1.0 mmol/l (mean +/- SEM) (p less than 0.01) and reduced intraerythrocytic potassium from 100.1 +/- 1.3 to 95.9 +/- 1.8 mmol/l (p less than 0.01). These changes were strongly correlated with the steady-state plasma digoxin concentration. During a few weeks of digoxin therapy, the intraerythrocytic cation composition normalized gradually. In patients on chronic treatment, neither intraerythrocytic sodium (11.3 +/- 0.3 mmol/l) nor potassium concentrations (100.0 +/- 0.6 mmol/l) differed significantly from the values of the control group (11.4 +/- 0.2 and 99.9 +/- 0.5 mmol/l, respectively). The changes in intraerythrocytic cation concentrations, induced by acute digitalization, seem to disappear during chronic administration of the drug.

Aged↗
PubMed1981

Digoxin-verapamil interaction.

To explore a possible interaction between digoxin and verapamil, a single-dose kinetic study of digoxin was performed and then repeated after 10 days of verapamil treatment in eight healthy subjects. Verapamil diminished the apparent central distribution volume of digoxin from 0.83 +/- 0.25 to 0.64 +2- 0.17 l/kg (P less than 0.05) and reduced total body clearance of digoxin from 3.28 +/- 0.58 to 2.15 +/- 0.66 ml/min/kg (P less than 0.001) by impairing both renal and extrarenal clearance. Biological digoxin half-life rose from 38.6 +/- 8.5 to 50.5 +/- 8.3 hr (P less than 0.005). Reduction of renal clearance of digoxin may be due to inhibition of tubular secretion. The underlying mechanisms of extrarenal interaction are not known, but impaired hepatic degradation of digoxin induced by verapamil should be considered.

Adult↗
PubMed1980

The effect of quinidine on digoxin kinetics in cardiac patients.

The pharmacokinetics of digoxin was studied in 11 subjects before and during quinidine treatment. Renal clearances of digoxin and creatinine were calculated from plasma concentrations and urinary excretions of digoxin and creatinine in subjects on long-term digoxin treatment. The investigations were repeated in the same subjects during administration of quinidine. Renal clearance of digoxin decreased, while plasma concentration of digoxin and renal excretion of digoxin increased in the presence of quididine, indicating substantial changes of digoxin kinetics, induced by quinidine. The reduction in renal clearance of digoxin may be due to a specific inhibition of tubular secretion of digoxin. The considerable rise of the plasma digoxin level and the increased excretion of digoxin support the assumption of a major extrarenal mechanism of interaction.

Aged↗