Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Digoxin”

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.

At least 1,063 records · Page 59Linked to original sources
PubMed1976

[Salivary electrolytes and serum digoxin in the Assessment of digitalis intoxication (author's transl)].

Salivary electrolytes (potassium and calcium), as well as serum digoxin levels were measured in 114 patients receiving digoxin or one of its derivatives. The mean value of the product of salivary potassium (mVal/I) and calcium (mVal/i in digoxin-treated patients without signs of digitalis intoxication (group 1) was 235 +/- 137 (SD) and with digitalis intoxication (group 2) 404 +/- 161 (SD). The difference in these values was not of statistical significance. The mean serum digoxin levels were 1.38 +/- 0.6 ng/ml (SD) in group 1 and 2.97 +/- 0.7 ng/ml (SD) in group 2; this difference is highly significant (p less than 0.001). Both salivary electrolytes and serum digoxin levels were falsely elevated in 11% of group 1 patients. 50% of the cases in group 2 showed salivary electrolyte values within the range of group 1, but there was only 1 patient with a serum digoxin level of below 2 ng/ml. It can, thus, be concluded that measurement of the salivary electrolytes is a test of only limited value in the assessment of digitalis intoxication, whereas determination of the serum digoxin level is a valuable diagnostic tool.

Calcium↗
PubMed2001

Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies.

Drug delivery across the blood-brain barrier is limited by several mechanisms. One important mechanism is drug efflux, mediated by several transport proteins, including P-glycoprotein. The goal of this work was to examine the effect of a novel drug delivery system, Pluronic block copolymer P85, on P-glycoprotein-mediated efflux from the brain using in vitro and in vivo methods. The hypothesis was that specific Pluronic copolymer systems enhance drug delivery to the central nervous system through the inhibition of P-glycoprotein. The effect of P85 on the cellular accumulation and transport of digoxin, a model P-glycoprotein substrate, was examined in porcine kidney epithelial cells (LLC-PK1) transfected with the human MDR1 gene. The effect of P85 on the directional flux across an in vitro BBB was also characterized. In vivo brain distribution studies were accomplished using wild-type and P-glycoprotein knockout mice. Pluronic increased the cellular accumulation of digoxin 3-fold in LLC-PK1 cells and 5-fold in the LLC-PK1-MDR1-transfected cells. Similar effects were observed for a prototypical P-glycoprotein substrate rhodamine-123. P85 treatment decreased the basolateral-to-apical and increased the apical-to-basolateral digoxin flux across LLC-PK1-MDR1 cell monolayers, and analogous results were observed with the in vitro BBB monolayers. The coadministration of 1% P85 with radiolabeled digoxin in wild-type mice increased the brain penetration of digoxin 3-fold and the digoxin level in the P85-treated wild-type mice was similar to that observed in the P-glycoprotein-deficient animals. These data indicate that Pluronic P85 can enhance the delivery of digoxin to the brain through the inhibition of the P-glycoprotein-mediated efflux mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Clarithromycin-induced digoxin toxicity: a case report and a review of the literature.

A 70-year-old woman with a history of atrial fibrillation, on digoxin, presented with nausea, vomiting, and dizziness two days after initiation of clarithromycin therapy. Laboratory results revealed a serum digoxin level of 3.9 ng/ml (normal range 0.5-2.0) and creatinine of 1.1 mg/dl. The patient was admitted to the hospital and digoxin and clarithromycin were discontinued. The patient's symptoms were resolved within 24 hours and her serum digoxin level was 1.9 on the second hospital day. A review of recent literature suggests that clarithromycin may induce digoxin toxicity by three different mechanisms, including reduction of renal excretion of digoxin, alteration of intestinal flora, and inhibition of cytochrome P-450 in the liver. Digoxin toxicity was reported three to 17 days after the initiation of clarithromycin (8.1 +/- 4.8 days, n = 9). The wide variation in the time required for the appearance of toxicity may imply the different mechanisms involved in each case.

Aged↗
PubMed1975

The reactivity of derivatives of digoxin and digitoxin as measured by the Na-K-atpase displacement assay and by radioimmunoassay.

Derivatives of digoxin and digitoxin were measured by the Na-K-ATPase displacement assay and by radioimmunoassay and the data compared with biological potency of these compounds. There was a slightly higher affinity of digoxigenin-bis-digitoxoside as compared with digoxin using digoxin-specific antiserum and considerably less affinity of digoxigenin and dihydrodigoxin than the parent compound in the same system. A similar trend was observed for the derivatives of digitoxin using digoxin-specific antiserum. The recovery on extraction of some of the derivatives of digoxin and digitoxin differed from that of the parent compounds in the ATPase assay. The potency of the derivatives of these drugs in displacing 3H ouabain also differed from the parent compoundmboth the recovery on extraction and the potency for displacing ouabain must be considered in the estimation of the contribution of the derivatives of digoxin or digitoxin to the result of Na-K-ATPase assay. Quantitative information of the metabolites of digoxin and digitoxin in normal and pathological conditions is needed to properly interpret assay data obtained either by radioimmunoassay or by ATPase assay.

Adenosine Triphosphatases↗
PubMed2003

[Clinical study on effect of shengmai injection on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure].

OBJECTIVE: To investigate the effect of Shengmai Injection (SMI) on serum concentration and pharmacokinetic parameters of digoxin in patients with congestive heart failure. METHODS: Forty in-patients with congestive heart failure were selected and randomly divided into 4 groups, the three treated groups I, II and III treated with digoxin combined with 20 ml, 40 ml and 60 ml of SMI respectively, and the control group, 10 patients in each group. The serum concentration of digoxin at different time points was determined with radioimmunoassay and the pharmacokinetical parameters were calculated with 3P97 pharmacokinetic software. RESULTS: The serum concentration of digoxin in the treated group I was significantly lower than that in the control group (P < 0.05), with the pharmacokinetical parameters, including the elimination half-life time (T1/2), elimination rate constant (Ke), apparent volume of distribution (Vd), plasma clearance (CL) and area under curve (AUC), significantly different to those in the control group (P < 0.05 or P < 0.01). But the serum concentration of digoxin with its pharmacokinetical parameters in the other two treated groups were not different significantly to those in the control group respectively (P > 0.05). CONCLUSION: SMI could influence the metabolism of digoxin in patients with congestive heart failure. This study has provided an important reference for safe and rational combined use of digoxin and SMI in clinical practice.

Adult↗
PubMed1992

[Combination of oral administration of cibenzoline and digoxin in patients with supraventricular arrhythmia].

Chronic co-administration of digoxin and several antiarrhythmic drugs increases digoxin plasma levels. To determine the effects of the administration of oral cibenzoline on digoxin plasma levels and its effects on clinical and electrocardiographic parameters, we conducted a prospective multicenter study in 22 cardiac patients with a mean age of 66 +/- 12 years (39-85), who were on long term digoxin therapy (0.25 mg once daily for at least 2 weeks) and who required oral cibenzoline therapy in the prevention of recurrence of symptomatic atrial tachyarrhythmias. Cibenzoline was given for 4 weeks at a dose of 130 mg twice daily in patients aged less than 70 years (group I, n = 15) and this dosage was reduced by half in patients over 70 years of age (group II, n = 7). Evaluation of the effects of this combination on clinical and electrocardiographic tolerability as well as the drawing of blood samples for assay of cibenzoline and digoxin took place before and after 4 weeks treatment with cibenzoline. The digoxin plasma levels were (mean +/- sem) 0.96 +/- 0.1 ng.ml-1 before cibenzoline administration and remained unchanged after 4 weeks of combination therapy (1.0 +/- 0.1 ng.ml-1), p > 0.05. Digoxin plasma levels in group I varied from respectively 0.8 +/- 0.1 ng.ml-1 (0.5-1.7) to 0.8 +/- 0.1 ng.ml-1 (0.4-1.5) and in group II from 1.2 +/- 0.2 ng.ml-1 (0.6-2) to 1.4 +/- 0.3 ng.ml-1 (0.7-2.5). This therapy was well tolerated in 16 patients out of 21 evaluable patients (76%) and there was no significant change in vital signs during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1).

This article represents the first evidence that the renal secretion of the commonly used drug, digoxin, is mediated by P-glycoprotein. In this study, it was demonstrated that digoxin is a substrate of P-glycoprotein, and the mechanism of a clinically important drug interaction, such as digoxin-quinidine, was elucidated. Human P-glycoprotein was expressed on the apical membrane of the porcine kidney epithelial cell line, LLC-PK1 by transfecting with human MDR1 cDNA. The expression and function of P-glycoprotein were confirmed by Southern and Western blotting, RNase protection assay, immunostaining and transporting activity for vinblastine. The transepithelial transport of [3H]digoxin was measured across the cell monolayers grown on microporous polycarbonate membrane filters. The transfectant cells exhibited markedly greater basal-to-apical transport and less apical-to-basal transport than the host cells, and the former was 8-fold greater than the latter. The augmented transepithelial transport resulted from the increased efflux from cells to apical side. This oriented transport was inhibited by the presence of 20 microM vinblastine, quinidine or verapamil. The rate of efflux to the apical side was 2-fold greater than that to the basal side. Quinidine inhibited the efflux to the apical side but did not affect transport into the basal side. These findings demonstrate that digoxin is transported by human P-glycoprotein, which is a previously undiscovered drug transport system in the kidney other than organic cation and anion transport systems, and suggest a molecular mechanism for the renal tubular secretion of digoxin as well as clinically important digoxin-quinidine interaction via P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Cross-reactivity of anti-digoxin antibodies with digitoxin depends on tracer structure.

The most common methods for measuring digoxin concentrations in serum are immunoassays. The prerequisite for exact determination of the digoxin value is an antibody that specifically binds digoxin. Because digitoxin differs from digoxin only in the C-12 hydroxy group, it is difficult to obtain anti-digoxin antibodies that do not cross-react with this compound. During the development of a fluorescence polarization immunoassay (FPIA) for digoxin, we investigated digoxin tracers with different structures. We found that in FPIA the digitoxin cross-reactivity of an antibody could be reduced by varying the structure of the tracer molecule.

Animals↗
PubMed1992

Evaluation of the CEDIA digoxin assay on Boehringer Mannheim/Hitachi 717 analyzer.

Some aspects of a new homogeneous enzyme immunoassay for the determination of digoxin have been evaluated, as part of a multicenter project. The CEDIA Digoxin assay is based on the use of two beta-galactosidase fragments (EC 3.2.1.23) produced by recombinant DNA techniques, one of them linked to digoxin. These two fragments couple to form the complete active enzyme, if not hindered by anti-digoxin antibodies. Digoxin in serum competes for antibody binding. The procedure can easily be automated and does not require special equipment. The imprecision of the method was studied at three different concentration levels (0.56, 1.29 and 2.77 ng/mL of digoxin). Within-run coefficients of variation were 8.01%, 5.57% and 3.30%, respectively, the corresponding between-day CVs being 17.4%, 8.41% and 4.89%. The procedure was found to be linear up to 4.4 ng/mL. Reagents were stable for at least four weeks. Results obtained by the CEDIA Digoxin assay compared well with those obtained by fluorescence polarization immunoassay.

Digoxin↗
PubMed1991

[Evaluation of the use of digoxin in a primary care emergency service].

Digoxin is a widely used drug. Previous studies suggest a high prevalence of inadequate use, subtherapeutic levels and high toxicity rates. The aim of the present study was to evaluation the use of digoxin in our area. 50 consecutive patients who attended our emergency service and who were receiving digoxin on a chronic basis were prospectively evaluated. There were 37 females and males, with age 78.1 +/- 8.6 years. We found that digoxin was not indicated in 12% of cases. Only 48% had digoxin plasma levels within the therapeutic range. When plasma levels were considered in association with clinical and electrocardiographic findings, 12% of patients were undertreated and 6% had digitalis toxicity. There was no relation between the digoxin plasma level and the dosage schedule, the ECG findings, the renal function, the use of other drugs or the anthropometric data. Emphasis is made on the need to individualize digoxin therapy and to measure plasma levels in particular cases.

Aged↗
PubMedDate not supplied

Digoxin enhances bupivacaine toxicity in rats.

The influence of digoxin on the systemic toxic effects of bupivacaine was studied in a rodent animal model. The experiment was undertaken with consideration to clinical situations such as pregnancy that are associated with the secretion of an endogenous digoxin-like factor. Twenty Wistar male rats, under barbiturate anesthesia and controlled ventilation, received either 5 micrograms/kg intravenous digoxin (n = 10) or saline (n = 10), blinded to the observer. Digoxin serum concentration was 1.8 +/- 0.24 ng/ml in the study group. Thirty minutes after digoxin or saline was administered, bupivacaine was infused at a constant rate of 2mg/kg/minute. The threshold doses of bupivacaine toxic effects (first ventricular arrhythmia, 25% fall of baseline heart rate, 25% fall of baseline mean arterial blood pressure, first seizure activity, isoelectric electroencephalogram, and asystole) were significantly lower in the digoxin group, as were the lethal bupivacaine serum concentrations. Digoxin, in hyperoxic nonacidotic rats, increases the cardiac and central nervous system toxicity of bupivacaine. Based on the known electrophysiologic actions of these two drugs, a synergistic toxic interaction is demonstrated.

Animals↗
PubMed1991

Digoxin-like immunoreactivity in serum from neonates and infants reduced by centrifugal ultrafiltration and fluorescence polarization immunoassay.

We evaluated the TDx Digoxin II (Abbott) modified procedure for interference from digoxin-like immunoreactive factors (DLIF) in pediatric patients. The effectiveness of centrifugal ultrafiltration as a means of removing DLIF interference from the serum of such patients was assessed. We used sera from 40 patients who had not received digoxin, whom we divided into two age groups: 30 neonates (less than 34 days postpartum) and 10 infants (younger than six months). Digoxin-like immunoreactivity was detected in 34 of 41 (83%) neonatal specimens (range 0.2-1.0 micrograms/L) and 16 of 25 (60%) infants' specimens (range 0.2-1.3 micrograms/L). Centrifugal ultrafiltration of serum specimens from these patients reduced but did not eliminate the DLIF interference in some specimens. A comparison of concentrations of DLIF in serum with various other patients' characteristics demonstrated a strong correlation (r = 0.915; P = 0.0001) between DLIF and serum bilirubin in the infants. Apparent digoxin concentrations from 19 serum and serum ultrafiltrate samples collected from 13 patients (four neonates and nine infants) who were treated with digoxin showed a good correlation (r = 0.97); however, the serum samples showed a positive bias of 0.39 microgram/L. We conclude that the TDx Digoxin II modified procedure is still subject to considerable DLIF interference in these two pediatric populations. This interference can be reduced in some serum specimens, but cannot be eliminated completely as others reported.

Aging↗
PubMed1991

Altered hapten recognition by two anti-digoxin hybridoma variants due to variable region point mutations.

Two spontaneous variants of the murine anti-digoxin antibody-producing hybridoma cell line 26-10 were isolated by two-color fluorescence-activated cell sorting on the basis of altered hapten binding. The variable region sequences of the antibodies produced by the mutant lines revealed that each contains a single amino acid change in the heavy chain second complementarity determining region. A Tyr to His change at position 50 leads to a 40-fold reduction in affinity for digoxin. A Ser to Phe mutation at position 52 results in a 300-fold reduction in affinity for digoxin. A competition assay involving 33 digoxin analogues was used to examine the specificity of hapten binding of 26-10 and the two mutant antibodies. The position 50 mutant has a distinct specificity change; it exhibits a preference for digoxin congeners containing a hydroxyl group at the steroid 12 position, whereas the 26-10 parent does not. The affinities of all three antibodies for hapten are progressively lowered by substitutions of increasing size at the digoxin steroid D ring 16 position. Although 26-10 binds digoxin and its genin form equally, 12 and 16 steroid position substitutions which lower affinity also confer a preference for a sugar at the steroid 3 position. These results suggest that position 50 contributes to specificity of the antibody and that alterations of the hapten can lead to differences in recognition, possibly through a shift in hapten orientation within the binding site.

Amino Acid Sequence↗
PubMed1991

The transport of digoxin across the perfused human placental lobule.

The cardiac glycoside, digoxin, is clinically used to treat fetal tachyarrhythmias and congestive heart failure. The time course of digoxin transfer across the human placenta was studied by dually perfusing an isolated lobule of the human placenta in vitro. Viability of the placental preparation was validated by measuring the rates of glucose and oxygen consumption, lactate production and synthesis of the protein hormone, chorionic gonadotropin. Following administration of 5 ng/ml digoxin to the maternal circulation, digoxin appeared in the fetal circulation within 5 min. The disappearance of digoxin from the maternal circulation was biexponential and best fit a two-compartment pharmacokinetic model. Mean calculated volume of the central compartment (257 +/- 6.3 ml) was consistent with the actual volume of the in vitro maternal circulation (246 +/- 7.4 ml). The half-life of the distribution phase was 9.7 +/- 3.3 min, and half-life of the terminal elimination phase was 362 +/- 83 min. After 30 min of perfusion, the amount of digoxin leaving the maternal circulation and appearing in the fetal circulation was constant at a fetomaternal mass ratio of 0.36 +/- 0.04. This ratio was maintained through to the end of the 3-hr experiment. All of the digoxin leaving the maternal circulation could be accounted for either in the fetal circulation or bound to placental tissue. The time to achieve equal concentrations on both sides of the placenta was estimated to be 268 +/- 34 min. These data are consistent with in vivo data obtained in humans, and support the relevance of using the in vitro placental perfusion model to obtain information regarding placental drug transfer in humans.

Digoxin↗
PubMedDate not supplied

[The use of digitalis: a prospective study on the posology of digoxin with weekly interruption].

The dixogin dosage with an interruption of two consecutive days a week is frequently used in our country. We decided to compare this kind of digoxin dosage with an uninterrupted one by means of describing in each case the serum digoxin level, by determining whether it is in the so-called therapeutic range (0.8-2.0 ng/ml) or not, and by correlating the serum level to the clinical response (the control of heart rate in patients with atrial fibrillation). We designed a crossover clinical trial on 14 patients taking digoxin, having normal renal function and suffering from atrial fibrillation. The serum digoxin concentration found in the weekly interruption digoxin dosage (1.02 +/- 0.23 ng/ml before and 0.66 +/- 0.15 ng/ml after) was lower than one found in the continuous dosage (1.09 +/- 0.23 ng/ml). The 25% of the patients (before the interruption) and 75% (after the interruption) had plasma levels lower than 0.8 ng/ml, in opposition to the 8.3% found in the uninterrupted dosage. No patient on the continuous dosage showed clinical and/or electrocardiographic signs of digoxin toxicity. The mean heart rate was higher in the weekly interruption dosage (74.4 +/- 11.6 beats/min before and 83.9 +/- 6.4 beats/min after) than in the continuous dosage (72.9 +/- 10.5 beats/min). In terms of achieving serum digoxin levels within the so-called therapeutic range, the uninterrupted dosage proved to be better than the discontinuous one as well as to control the heart rate.

Atrial Fibrillation↗
PubMed1990

Understanding digoxin use in the elderly patient.

There are many disease states in the elderly that mandate the use of drugs with extremely narrow therapeutic indexes and potentially fatal toxicity. Digoxin is one example of such drugs. It is extensively used for the treatment of congestive heart failure of diverse origin and of cardiac arrhythmias of supraventricular origin. Aging can produce changes in essentially all organ systems, which as a whole render geriatric patients particularly vulnerable to the toxic effects of digoxin. Among all age-related pharmacokinetic and pharmacodynamic changes, declining renal function is perhaps the most important factor that must be considered. This often means a significantly less efficient renal digoxin clearance, which necessitates a reduction in dosage. The geriatric population tends to consume more drugs and are more at risk for undesirable multidrug interactions than their younger counterparts. To name a few, quinidine, verapamil, amiodarone, and non-K(+)-sparing diuretics are notorious for predisposing the patient to digoxin toxicity when administered concurrently with digoxin. Therefore, digoxin must be prescribed to elderly patients with great judiciousness, with careful interpretation of serum digoxin assay, and due consideration of its intrinsic limitations.

Aged↗
PubMed1990

[Results of treatment for severe congestive heart failure with digoxin, furosemide and vasodilating agents].

In 61 patients with class IV (NYHA) of chronic congestive cardiac failure treated for 2 weeks with digoxin (0.290 +/- 0.108 mg/d) and furosemide (13.0 +/- 4.1 mg/d), for 2 weeks with digoxin, furosemide and isosorbide dinitrate (44.5 +/- 9.8 mg/d) or nifedipine (42.0 +/- 12.2 mg/d), for 4 weeks with digoxin, furosemide, isosorbide or nifedipine and captopril (angiotensin converting enzyme inhibitor) (75.1 +/- 24.4 mg/d), and for the last 2 weeks with digoxin, furosemide, isosorbide or nifedipine without captopril, after each stage the clinical state, exercise tolerance and haemodynamic parameters determined echocardiographically were assessed. Ten weeks of treatment by this method caused regression of pulmonary congestion in 80%, oedema in 63.3% and hepatomegaly in 33.3% of the patients. Moreover, 60.7% of the patients returned to class III, 13.1% to class II, and 26.2% remained in class IV (NYHA). In the group treated with digoxin, furosemide, nifedipine with captopril (n = 30) a significant rise was observed of the value of the ejection fraction and cardiac index in relation to the treatment with digoxin and furosemide and the treatment with digoxin, furosemide, nifedipine (p less than 0.05). No drug improved significantly the tolerance of submaximal exercise. During the treatment with captopril no clinical improvement was achieved in 4 cases, and worsening occurred in 3 cases of severe cardiac failure (7 of 61 patients, 11.5%). The obtained results showed that vasodilating drugs are safe in congestive cardiac failure and in many cases of severe failure captopril contributed to rapid clinical and haemodynamic improvement.

Adult↗
PubMed1988

Effect of digoxin on the extent of injury and the severity of arrhythmias during acute myocardial ischemia and infarction in the dog.

Recently, this laboratory has demonstrated an enhanced susceptibility toward the development of lethal ventricular arrhythmias occurring in response to acute posterolateral ischemia in dogs with previous anterior myocardial infarction in the presence of therapeutic serum concentrations of digoxin. In the present study, acute posterolateral myocardial ischemia was produced in the absence of previous myocardial infarction in 15 digoxin-pretreated (1.19 +/- 0.21 ng/ml serum digoxin, 5-7 days pretreatment) and 11 vehicle-pretreated dogs. The incidences of sudden ventricular fibrillation and of 24 h arrhythmic mortality in response to posterolateral ischemia were 4/15 (27%) vs. 1/11 (9%) (p = 0.23) and 7/15 (47%) vs. 4/11 (36%) (p = 0.27) for digoxin- vs. vehicle-pretreated dogs, respectively. Ventricular ectopic activity at 24 and 48 h after the onset of posterolateral ischemia was reduced significantly by both intravenous lidocaine (1.0-5.0 mg/kg) and verapamil (50.0-500.0 micrograms/kg) in the vehicle-pretreated dogs, whereas neither antiarrhythmic agent significantly suppressed ventricular ectopy in the digoxin-pretreated dogs. The mean sizes for developing posterolateral myocardial infarctions (percentage of left ventricle) were greater for the digoxin-pretreatment group (31.9 +/- 2.8%) vs. vehicle-pretreatment group (14.8 +/- 2.0%, p less than 0.001). These findings suggest that uncomplicated acute myocardial ischemia in the presence of serum concentrations of digoxin that are considered clinically therapeutic may result in the development of larger areas of developing myocardial infarction and in the occurrence of ventricular arrhythmias that are less sensitive to suppression with conventional antiarrhythmic agents.

Animals↗