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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 263-270 
    ISSN: 1432-1041
    Keywords: digoxin ; quinidine ; ouabain ; cell binding constants ; lymphocytes ; mononuclear cells ; drug interaction ; glycoside receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 31 (1986), S. 91-94 
    ISSN: 1432-1041
    Keywords: oxcarbazepine ; epilepsy ; saliva ; protein binding ; drug monitoring ; 10-OH-carbazepine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The utility of saliva sampling in monitoring oxcarbazepine therapy has been assessed in 17 epileptic outpatients treated with a mean dose 22.7 mg/kg/d for 19–411 days, i. e. at steady-state. Blood was collected before the morning dose measurement of the plasma 10-OH-carbazepine concentration and determination of the protein bound fraction. Immediately after blood sampling resting saliva and saliva produced after a masticatory stimulus were collected. Using equilibrium dialysis and an ultrafiltration technique the protein binding of 10-OH-carbazepine was found to be 40% and 45%, respectively. When the degree of protein binding was expressed as the ratio between the corresponding saliva and plasma concentrations of 10-OH-carbazepine, the concentration in resting saliva indicated that no drug was bound to plasma protein, whereas the use of stimulated saliva suggested a protein-bound fraction of 35%. The concentration in stimulated saliva reflects the free fraction of 10-OH-carbazepine, but regression analysis of paired salivary and plasma values showed that the prediction of plasma concentrations from levels in saliva is uncertain. This, together with the low degree of plasma protein binding, leads to the conclusion that it would be preferable to monitor total plasma concentrations if therapeutic drug monitoring of oxcarbazepine were to prove essential in epileptic patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: amitriptyline ; imipramine ; clomipramine ; antidepressant overdose ; clinical effects ; pharmacokinetics ; cardiotoxicity ; maprotiline ; doxepine ; nortriptyline ; opipramol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24 h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 µg/l, with concentrations above 500 µg/l in 11 cases. The serum amitriptyline concentration remained high for 3–4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 µg/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidpressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60–500 µg/l) but not high (〉500 µg/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 41-47 
    ISSN: 1432-1041
    Keywords: quinidine ; digoxin ; interaction ; kinetics ; absorption ; elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 447-453 
    ISSN: 1432-1041
    Keywords: atrial fibrillation ; verapamil ; slow-release formulation ; Holter monitoring ; multiple drug intake ; plasma level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 613-615 
    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Circadian variation in the metabolism of verapamil was investigated in 10 patients with stable angina pectoris during treatment with sustained-release verapamil 360 mg at 08.00 h or 22.0 h. No major difference in exercise parameters was found. During the evening dosage schedule a significantly greater bioavailability (AUC) and a prolonged time to peak concentration was found. During the night (24.00 h–06.00 h) the half-life of verapamil was significantly longer than during the day (16.00 h–22.00 h). These differences in pharmacokinetics may be due to reduced hepatic blood flow at night or to circadian variation in hepatic microsomal metabolism.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 303-305 
    ISSN: 1432-1041
    Keywords: Bartter's syndrome ; Hypokalaemia ; Captopril ; ACE-inhibitor ; lymphocyte sodium and potassium ; adverse effect ; plasma renin ; aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol·l−1) and a mean serum renin of 217 mU·l−1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol·l−1, which rose to 3.4 mmol·l−1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol·l−1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 609-611 
    ISSN: 1432-1041
    Keywords: Digitalis ; Exercise ; hyperkalaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 9 patients with atrial fibrillation the effect of zero, low and high levels of serum digoxin on exercise-induced hyperkalemia was assessed by bicycle exercise tests. Exercise at each level of serum digoxin was associated with a significant (up to 20%) rise in plasma potassium. At a work load of 75 W the highest level of serum digoxin was associated with a significantly higher maximum plasma potassium concentration as compared to the maximum valueatazero serum digoxin. The enhancement of exercise-induced hyperkalemia may add to the arrhythmogenic effect of digitalis.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 15 (1979), S. 63-68 
    ISSN: 1432-1041
    Keywords: procainamide ; N-acetylprocainamide ; arrhythmia ; acetylator phenotype ; antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to estimate the relative antiarrhythmic effect of procainamide and N-acetylprocainamide, 18 randomly selected, patients with arrhythmia were divided into two groups; the first was treated with Pronestyl® in the first half of the investigation period, followed by Duretter® in the second half, and the second group began with Duretter® and terminated with Pronestyl®. The concentrations of procainamide and N-acetylprocainamide were measured twice a day during the steady state part of each treatment period. The acetylation phenotype of the patients was determined with sulfadimidine, and was compared with the relative serum concentrations of procainamide and N-acetylprocainamide. N-acetylprocainamide was found to antagonize the action of procainamide.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1041
    Keywords: digoxin ; verapamil ; digoxin-verapamil interaction ; kinetics ; plasma level ; renal clearance ; extra-renal clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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