SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The effect of dofetilide on the steady-state pharmacokinetics of digoxin was evaluated in a randomized, double-blind study. Five days of dofetilide treatment did not significantly affect steady-state pharmacokinetic variables of digoxin compared with placebo; therefore, the use of dofetilide does not necessitate an adjustment in digoxin dose to maintain therapeutic digoxin levels.
There is increasing evidence that clinical deterioration in manifest chronic heart failure is related to both hemodynamic and neurohumoral factors. Only few data are available, however, on the progression of disease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the influence of drugs that may affect these variables. Accordingly, we studied 64 patients with heart failure who were in New York Heart Association functional class II (88%) and III (12%). They were randomized to double-blind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). Their age (mean +/- SD) was 60 +/- 8 years, and left ventricular ejection fraction (mean +/- SD) was 0.33 +/- 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p = NS between groups). Exercise time decreased in patients treated with placebo after 6 months (median -62 seconds; p < 0.05 vs baseline), but it increased with ibopamine (+48 seconds), and digoxin (+17 seconds; both p < 0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median + 31 pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p < 0.05 vs placebo). Plasma renin and aldosterone levels were unchanged after 6 months in the placebo group, but digoxin therapy slightly reduced plasma renin concentration (-5 microU/ml; p < 0.05 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)
Supraventricular tachydysrhythmia is a bothersome and potentially harmful occurrence after coronary artery bypass graft operation (CABG). Use of digoxin prophylaxis preoperatively has yielded conflicting results in lowering the incidence of supraventricular tachydysrhythmia. In this study, three groups of patients were formed. Group 1 served as the control; no prophylactic medication was given. Group 2 was given digoxin prophylaxis beginning immediately after operation. Group 3 received digoxin postoperatively as did Group 2, plus orally administered propranolol beginning on postoperative day 2. No difference in the incidence of supraventricular tachydysrhythmia was found between Groups 1 and 2 (28.2% versus 28.9%). However, the incidence in Group 3 was 2.2%, and this represented a statistically significant difference (p less than 0.005) compared with either Group or 2. The combined use of digoxin and propranolol postoperatively significantly reduced the incidence of supraventricular tachydysrhythmia after CABG.
We have biotinylated the terminal glycose of digoxin by reaction of the periodate-oxidized steroid with biotin hydrazide. A biotinylated product (BD-1) was formed which retained significant digoxin receptor (Na+/K+ ATPase) binding activity. Sustained reaction resulted in a second biotinylated product (BD-2) which showed reduced receptor binding activity. The products were characterized by FAB mass spectroscopy and shown to be the mono- and di-biotinylated digoxin conjugates of the oxidized glycose moiety. These analogues may prove useful in determining the subcellular site of digoxin binding.
The present study has examined the cross-reactivity of fatty acids and mono- and di-glycerides in the fluorescence polarization immunoassay for digoxin. The ability of these compounds to inhibit 86Rb uptake by the erythrocyte as well as their ability to displace 3H-ouabain from membrane-bound dog kidney ATP-ase was also assessed. Some unsaturated fatty acids (palmitoleic, palmitelaidic, oleic, linoleic, linolelaidic, linolenic, gamma-linolenic and arachidonic) were found to cross-react significantly in the digoxin immunoassay and to inhibit 3H-ouabain binding to membrane-bound Na+/K+-ATPase. Of the monoglycerides studied mono-11-eicosenoin was found to cross-react in the digoxin immunoassay, inhibit red cell 86Rb uptake and displace 3H-ouabain from its receptor, membrane-bound Na+/K+-ATPase. Two other monoglycerides, 1-monolinoleoyl and 1-monolinolenoyl glycerides, were able to displace 3H-ouabain from membrane-bound Na+/K+-ATPase, but had no effect on the digoxin immunoassay or on red cell 86Rb uptake.
Serum digoxin values were determined in a newborn infant with severe heart failure and renal failure. The half-life of digoxin in the serum appeared to change, possibly the result of prolonged distribution and/or absorption owing to circulatory insufficiency, or to the accumulation of cross-reacting metabolites of digoxin in the serum. No clinical toxicity was apparent, and no cardiac arrhythmia was observed. The need for monitoring serum digoxin concentration and clinical effect in newborn infants is emphasized.
We report the detection of a digoxin-like immunoequivalent substance in the plasma of neonates and infants and in amniotic fluid. Time-course studies in individual infants indicate that the substance probably is produced endogenously and is not exclusively retained by the infants from external sources. Digoxin recovery studies demonstrated that the presence of this material caused falsely elevated digoxin values. Our results cast considerable doubt on the reliability and clinical utility of digoxin radioimmunoassay measurements on the serum or plasma of neonatal and infant patients.
STUDY OBJECTIVE: To determine the relative effectiveness of a verapamil-quinidine sequential combination versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation (PAF). METHOD: This prospective, double-blind, randomized, controlled trial involved patients, aged 18 to 75 years, with new-onset (< 48 hours) atrial fibrillation who presented to a community-based urban hospital with an annual ED census of 65,000. Exclusion criteria included ventricular response rate lower than 100 or higher than 200 beats/minute, allergy to study drugs, hypotension with evidence of end-organ hypoperfusion, and conduction abnormalities. Consenting patients were randomly assigned to receive rapid digitalization (1.0 mg over 2 hours) or i.v. verapamil (sequential 5-mg boluses up to 20 mg). After ventricular rate was controlled (< 100 beats/minute), oral quinidine (200 mg) was initiated and repeated every 2 hours until conversion to normal sinus rhythm (NSR) occurred, until 1 g of quinidine was administered, or until adverse effects supervened. Heart rate, blood pressure, cardiac rhythm, time to conversion, and adverse effects were documented. RESULTS: Forty-four patients received the study drugs. Three were withdrawn, leaving 19 in the verapamil-quinidine (VER-Q) group and 22 in the digoxin-quinidine (DIG-Q) group. Sixteen patients (84%) in the VER-Q group and 10 (45%) in the DIG-Q group converted to NSR within 6 hours (P < .02). Mean time to conversion (+/-SD) was 185 +/- 146 minutes for VER-Q and 368 +/- 386 minutes for DIG-Q patients (P = NS). Twelve VER-Q patients (63%) and 6 DIG-Q patients (27%) were discharged from the ED (P < .05). Minor adverse effects were more common in the VER-Q group. No mortality or significant morbidity occurred. CONCLUSION: The sequential combination of verapamil and quinidine, in the doses studied, is an effective treatment for PAF and is superior to digoxin-quinidine. Digoxin should no longer be considered the treatment of choice for uncomplicated PAF.
A specific assay method for radiolabelled digoxin and its known apolar metabolites in plasma, urine and saliva was developed. The assay permits the delineation of the pharmacokinetics of digoxin and its metabolites after single-dose administration of the drug to humans. Column chromatographic and solvent extraction procedures were used for the separation of apolar and polar compounds. Thin-layer chromatography was applied for the individual and specific assessment of digoxin and its apolar metabolites. Apolar and polar standards were used for quantitative assessments of all the procedures used. Accuracy and precision of the assay developed were evaluated in plasma, urine and saliva using biological samples spiked with known amounts of standards and by measuring replicates of biological samples obtained from pharmacokinetic studies wit digoxin administration to humans.
High-performance liquid chromatographic (HPLC) systems are described for the separation of the cardioactive metabolites of the digoxin and digitoxin series that are formed by the splitting of digitoxose sugar residues from the aglycone steroid: isocratic separation of digoxin and its cardioactive metabolites; isocratic separation of digitoxin and its cardioactive metabolites; and gradient elution separation of the digoxin and digitoxin series including beta-acetyl- and beta-methyldigoxin. Separations were performed on a 10-microns bonded octadecyl phase column using various mixtures of acetonitrile--water and acetonitrile--methanol--water as the mobile phase. These methods provide high peak resolution and are well suited for collecting elution fractions, e.g. to link up with sensitive immunological measurements. An HPLC-radioimmunoassay method is described for the quantitation of digoxin, digitoxin and their metabolites in human tissues.
We present here a fatal poisoning case involving verapamil, metoprolol and digoxin. A 39-year-old male was found dead in his room, and a lot of empty packets of prescribed drugs were found near the corpse. The blood concentrations of verapamil, metoprolol and digoxin were 9.2 microg/ml, 3.6 microg/ml and 3.2 ng/ml, respectively. The cause of death was given as cardiac failure, hypotension and bradycardia due to a mixed drug overdose of verapamil, metoprolol and digoxin, based on the results of the autopsy and toxicological examination. We speculate that the toxicity of verapamil is potentiated by drug interaction with metoprolol and digoxin.
This is the first report in the forensic literature of a combination of fatal digoxin poisoning with endocardial fibroelastosis (EFE). Typical morphological features of EFE as the cause of clinically diagnosed cardiomyopathy were present in the autopsy of a 3-year-old girl, including cardiac hypertrophy and marked thickening of the left-sided endocardium, consisting of numerous elastic and collagenic fibres. After exclusion of cardiac and cerebral causes of death, accidental digoxin intoxication was proved. Postmortem toxicological analyses by fluorescence polarization immunoassay (FPIA) disclosed digoxin levels of 71 micrograms/kg (femoral vein blood), 77 micrograms/kg (cardiac blood), 255 and 221 micrograms/kg (cardiac muscle of the right and left chamber), 163 micrograms/kg (psoas muscle), 91 micrograms/kg (lung), 222 micrograms/kg (liver) and 520 micrograms/kg (kidney). The results are compared with the antemortem digoxin concentration of 39 ng/ml serum. The case is discussed from its unusual morphological and toxicological aspects, with special consideration of possible medical malpractice.
To assess the effects of digoxin as single therapy and in combination with quinidine in the treatment of atrial fibrillation, the atrial fibrillation threshold was determined from the right atrial appendage and Bachmann's bundle in 11 open chest dogs. In group 1 (six dogs), the atrial fibrillation threshold was determined at baseline, post-quinidine (10 mg/kg intravenously) and then post-digoxin (50 micrograms/kg intravenously). In group 2 (five dogs), the order of drug administration was reversed. The results of this study were: 1) Digoxin had no significant effect on the atrial fibrillation threshold when given alone. 2) Quinidine significantly increased the atrial fibrillation threshold (p less than 0.002) and the addition of digoxin resulted in a further increase in threshold (p less than 0.002). 3) Quinidine produced greater suppression of atrial fibrillation induction at the right atrial site than at the Bachmann's bundle site, suggesting differential effects of quinidine on atrial fibers.
The calcium channel blocking agents, verapamil and diltiazem, and the digitalis compound, digoxin, caused drug specific rate-dependent changes of the atrioventricular conduction time (AVCT). The purpose of this study was to investigate this rate adaptation of the AVCT in isolated guinea pig hearts perfused by the method of Langendorff to get an insight in drug-specific binding kinetic to the respective channel. In the presence of 10 nM verapamil, 30 nM diltiazem, or 0.6 nM digoxin, the atrioventricular conduction time was prolonged to a comparable degree during sinus rhythm. The drug-specific time constant, characterizing the rate-dependent adaptation of the AVCT, in the presence of a substance was comparable if evaluated after abruptly changing the heart rate from the pacing cycle length of 240 ms to 180 ms (tau-on) or from 180 to 240 ms (tau-off). The adaptation of the AVCT in the presence of verapamil (tau-on = 178 +/- 45 beats, tau-off = 125 +/- 33 beats, mean +/- SEM) was more pronounced than in the presence of digoxin (tau-on = 144 +/- 24 beats, tau-off = 98 +/- 15 beats) or diltiazem (tau-on = 70 +/- 11 beats, tau-off = 98 +/- 15 beats). In conclusion, the differences in the rate adaptation of the AVCT may be explained by the drug-specific association and dissociation kinetic to the calcium channel, slow in the case of verapamil, and fast in the case of dilitiazem, whereas this phenomenon in the presence of digoxin may be explained by its direct effects on passive membrane properties.
Patients suffering from manic-depressive psychosis, manic type (ICD 296.0), were treated with lithium carbonate and randomly allocated to two groups, one received digoxin and the other matching placebo for 7 days. Severity of mania was rated by psychiatrists on the Manic Rating Scale and Analogue Line on days 0 and 7 and by nurses daily on the Hargreaves Rating Scale, Psychotic Rating. Fourteen patients received digoxin and lithium carbonate and 14 patients received placebo and lithium carbonate. Improvement in the placebo lithium group was significantly greater than that in the digoxin lithium group. This trial suggests, therefore, that the effect of inhibition of membrane cation carrier is to reduce the response to lithium. This result is in keeping with our hypothesis that an increase in Na-K ATPase is essential to the therapeutic effect of lithium carbonate. It does not, however, exclude the possibility that the observations resulted from the inhibition by digoxin of lithium entry into the brain.
We evaluated the effects of long-term digoxin therapy on exercise capacity and on physiological parameters reflecting autonomic tone in 23 patients with mild to moderate heart failure. Before and after maintenance digoxin treatment, all patients underwent cardiopulmonary exercise testing and indexes of heart rate variability (HRV) and baroreceptor sensitivity (BRS) were measured. Long-term digoxin therapy significantly (P < 0.05) increased time domain indexes (rMSSD, pNN50) which reflect parasympathetic activity (from 30 +/- 16 to 37 +/- 14 and from 8 +/- 9 to 12 +/- 7, respectively). High-frequency (HF) and low-frequency (LF) power spectral components also showed a significant increase (from 4.5 +/- 1 to 5.1 +/- 1 and from 5.4 +/- 1 to 5.8 +/- 1, respectively), but the ratio LF/HF decreased, indicating a predominance of vagal activity. The magnitude of these changes exhibited a strong negative Pearson correlation coefficient when compared with initial values before treatment. BRS increased from 2.95 +/- 1.2 to 5.32 +/- 3 ms/mmHg (P < 0.05). Oxygen consumption at peak exercise and at the anerobic threshold increased significantly (from 17 +/- 3 to 19 +/- 3 mL/kg/min and from 14.7 +/- 3 to 16.5 +/- 3 mL/kg/min, respectively). A persistent negative correlation was found between initial values of HRV and the magnitude of changes in exercise capacity. These findings show that long-term digoxin therapy increases vagal activity and improves exercise capacity in patients with mild to moderate heart failure and seems to exert a more marked therapeutic effect on patients with poorer initial autonomic function.
PURPOSE: To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. METHODS: The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. RESULTS: It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C). 52.6% (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3% (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC0-4 h values (+/-SD) were 4.11 +/- 0.57, 3.20 +/- 0.49. and 3.27 +/- 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. CONCLUSIONS: The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.
PURPOSE: Recent clinical studies suggest the importance of the MDR1 genotype at position 3435 (C3435T) in terms of pharmacokinetics, but there is still no consensus in reports on the relationship between the genotype and plasma/serum concentration-time profiles of drugs after conventional oral administration. This study was performed to elucidate the effects of C3435T on the rate of duodenal absorption of digoxin in healthy Japanese subjects. METHODS: Digoxin solution was sprinkled directly over the surface of the duodenum using an endoscope, and its absorption rate was evaluated by serial monitoring of the serum concentration and by analysis of its initial 15-min increasing phase. RESULTS: The duodenal absorption rates of digoxin were 911 +/- 91 ng/min and 506 +/- 76 ng/min for C/C and T/T, respectively (+/- SE, p = 0.007). CONCLUSION: The C3435T mutation of the MDR1 gene is associated with suppression of duodenal absorption of digoxin.
Refine your search to explore more results.