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At least 595 records · Page 33Linked to original sources
PubMed1997

Digoxin-itraconazole interaction: possible mechanisms.

OBJECTIVE: To document a case in which the administration of itraconazole was associated with an apparent decrease in digoxin clearance, resulting in an increase in the serum digoxin concentration. CASE SUMMARY: A man receiving digoxin for atrial fibrillation was concurrently treated with itraconazole 200 mg/d for esophageal candidiasis. The estimated urinary digoxin clearance was decreased during this combination therapy. DISCUSSION: Digoxin is primarily cleared by the kidneys, and the mechanism of renal clearance involves both glomerular filtration and tubular secretion. We postulate that itraconazole or a metabolite of this compound may have resulted in decreased tubular secretion of digoxin, accounting for decreased urinary digoxin clearance. CONCLUSIONS: Monitoring of serum digoxin concentrations should be performed if patients taking digoxin are treated with itraconazole. Further investigation is necessary to elucidate the nature of the interaction between digoxin and itraconazole.

Aged↗
PubMedDate not supplied

Is there an expanded role for digoxin in patients with heart failure and sinus rhythm? A protagonist viewpoint.

The evidence supporting the efficacy of digoxin in patients with heart failure who are in sinus rhythm is substantial. Digoxin improves hemodynamics, exercise capacity, symptoms, and quality of life and reduces hospitalizations. All of this is accomplished with a drug that is very inexpensive and can be given once daily. Its safety has been established through the DIG trial. Although digoxin does not decrease mortality beyond that of diuretics and ACE inhibitors, it does not increase mortality, unlike many positive inotropes. Furthermore, digoxin, in addition to ACE inhibitors and a diuretic, decreases the hospitalization rate due to worsening of heart failure. From a managed care perspective, as well as that of the patient, this is of enormous benefit. A pharmacoeconomic analysis estimated that continuation of digoxin in patients with stable congestive heart failure could save the healthcare system an estimated $ 400 million, based on costs from one hospital. The issue is not whether to use digoxin in these patients, but rather, how early to initiate therapy. From some of the recent data in patients with systolic dysfunction and mild heart failure, as well as knowledge of the neurohormonal activation that occurs early in these patients, it could be suggested that early use of neurohormonal modulators, including digoxin, would decrease the progression of heart failure. Thus, rather than waiting for symptoms despite optimal doses of an ACE inhibitor and diuretic, as suggested by the AHCPR practice guideline for heart failure, initiation of digoxin therapy in patients as early as NYHA class II at a dosage that will achieve a serum concentration of 1.0 ng/mL or less should occur. With the understanding of digoxin's effect on the neurohormonal systems, its role in patients with preserved systolic function needs to be reexplored. The debate can now focus on asymptomatic patients or those with preserved systolic function. Could these patients benefit from therapy with digoxin as well?

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Differential pharmacokinetics of digoxin in elderly patients.

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.

Absorption↗
PubMed2004

Digoxin-specific antibody fragments: how much and when?

Digitalis glycoside poisoning is an important clinical problem and the development of digoxin-specific antibody fragments (Fab) 30 years ago has changed clinical practice. Nevertheless, doubts still exist as to the appropriate dose indications for therapy. This paper reviews relevant literature, describes the difficulties associated with current treatment protocols and proposes an approach to therapy, which is based on theoretical principles and evidence gleaned from currently available clinical data sets. In patients with 'acute' poisoning, serum digoxin concentrations do not equate to the total body burden, as tissue distribution will not have occurred, and the calculations for present protocols, which use serum concentrations, are therefore likely to result in too much antibody being administered. Since a therapeutic quantity of digoxin will have little effect in a normal individual, complete neutralisation of all digoxin is also unnecessary. The pharmacokinetic and dynamic logic of using a smaller initial loading dose than predicted from total body calculations is rational. It is recommended that half the calculated loading dose, either based on serum concentration or history, should be administered and the impact on clinical features observed. If a clinical response is not seen within 1-2 hours, a further similar dose should be given. In the event of a full response, patients should be monitored for 6-12 hours; a second dose should only be given in the event of recurrence of toxicity. In patients with 'chronic' digoxin poisoning, the serum digoxin concentration will reflect the total body load. However, since such patients are invariably receiving digoxin for therapeutic purposes, full neutralisation is again not indicated. In addition, tissue redistribution of digoxin from deeper stores will occur following the binding of biologically active digoxin in the circulation. This process will occur over a number of hours and if the total calculated dose of antibody is administered in a single bolus, significant quantities will be excreted prior to redistribution of digoxin. Pharmacokinetic logic, therefore, suggests that half the calculated loading dose, based on serum concentration, should be administered and the impact on clinical features observed; a second dose should be given in the event of recurrence of toxicity.

Digoxin↗
PubMed2002

Do therapeutic doses of acarbose alter the pharmacokinetics of digoxin?

BACKGROUND: Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation. OBJECTIVE: To evaluate a possible drug interaction between acarbose and digoxin. METHODS: An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period II, they were given acarbose tablets, 50 mg 3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval. Serum digoxin levels, over time, in the two periods were compared by standard techniques. RESULTS: There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence and absence of acarbose, were 2.89 and 2.40 g/L respectively (P = 0.05). Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window. CONCLUSION: There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.

Acarbose↗
PubMed2003

[Digoxin plasma levels in four different prescription schedules of common use in clinical practice].

BACKGROUND: The different therapeutic schedules used for the prescription of digoxin have little theoretical support. AIM: To measure digoxin plasma levels in patients using four different prescription schedules. PATIENTS AND METHODS: Four groups of patients were studied. Group I corresponded to 56 patients taking digoxin 0.25 mg/day, from Monday to Friday. Group II corresponded to 30 patients taking digoxin 0.25 mg/day, from Monday to Saturday. Group III corresponded to 53 patients taking digoxin 0.25 mg/day continuously. Group IV corresponded to 36 patients taking digoxin 0.125 mg/day continuously. Plasma digoxin levels were measured in two consecutive Mondays before taking the daily dose of the drug. Serum creatinine was also measured and creatinine clearance was calculated. The therapeutic plasma concentration range was set between 0.5 and 2 ng/ml. RESULTS: Mean plasma digoxin levels were 1.15 +/- 0.8 ng/ml in group I, 1.4 +/- 0.55 ng/ml in group II, 1.68 +/- 0.7 ng/ml in group III and 1.14 +/- 0.43 ng/ml in group IV. 93% of patients in group I, 80% of patients in group II, 75% of patients in group III and 94% of patients in group IV had therapeutic digoxin levels. A low creatinine clearance, an age over 65 and interactions with other drugs were risk factors associated with supratherapeutic levels, mostly seen in group II and group III with 20% and 24% respectively. CONCLUSIONS: Most patients using digoxin with different therapeutic schedules had plasma drug levels within the therapeutic range.

Aged↗
PubMed1992

Improving the specificity of digoxin immunoassays.

The overall reliability of measuring digoxin in serum improved significantly with the discovery and application of immunoassays. However, because of the low concentration of digoxin being measured, its narrow therapeutic range in serum, and the presence of endogenous digoxin-like immunoreactive factors (DLIF), developing assays for measuring digoxin still pose formidable challenges. In this presentation, recent developments in the characterization of DLIF from bovine adrenal cortex and human serum are described. Data accumulated to date suggest there is one principal endogenous molecular factor (DLIF) in humans that cross-reacts with anti-digoxin antibodies. This factor exists at sufficiently high concentrations in some patients to interfere with measurements of digoxin by most digoxin immunoassays. All digoxin immunoassays should be tested to interference from this endogenous factor. Various techniques for reducing DLIF cross-reactivity are reviewed. The isolation and purification of DLIF now provides new approaches for selecting specific anti-digoxin antibodies used in developing more accurate digoxin immunoassays.

Blood Proteins↗
PubMed1991

Effect of enrofloxacin on digoxin clearance and steady-state serum concentrations in dogs.

The effect of enrofloxacin on the oral clearance and steady-state concentrations of digoxin in serum was evaluated in dogs. Digoxin was administered orally to six healthy adult Beagle dogs following a multiple-dose regimen of 0.0625 mg every 12 h for 23 days. From days 14 to 23 enrofloxacin was administered orally at a dosage of 2.5 mg/kg every 12 h, with subjects receiving enrofloxacin 2 h prior to digoxin. Trough serum concentrations of digoxin were measured using an immunoassay technique. On days 13 and 22, dogs were catheterized for multiple blood sample collection during the 12 h digoxin dosing interval and serum samples were analyzed for digoxin concentrations. In general, steady-state digoxin concentrations in trough serum were not significantly different during enrofloxacin treatment than before enrofloxacin administration. Similarly, digoxin oral clearance was not significantly different between pre-enrofloxacin and digoxin + enrofloxacin periods. We conclude that enrofloxacin is unlikely to have a significant impact on digoxin disposition in dogs.

4-Quinolones↗
PubMed1990

[Drug interaction between digoxin and bisacodyl].

Digoxin is one of the inotropic agents commonly used to improve cardiac performance in patients with congestive heart failure and to control ventricular response in atrial fibrillation and other supraventricular tachycardias. Bisacodyl (dulcolax), a stimulant laxative, is also commonly prescribed to prevent straining at stool or constipation in these patients. Therapeutic monitoring of digoxin is helpful in the evaluation of clinical response and intoxication of digoxin. For the convenience of serum level measurement, digoxin is usually administered at night before sleep to allow ample time for tissue distribution and then blood sampling the next morning. Concomitant use of these drugs may increase the likelihood of drug interaction. Eleven healthy volunteers, aged 22-26, were studied within 35 days accordingly in four phases. The serum digoxin concentration (SDC) in phase 2 (digoxin and bisacodyl together) showed a significant decrease as compared with phase 1 (digoxin alone) (0.58 +/- 0.03 vs. 0.66 +/- 0.03 ng/ml, M +/- SE, p less than 0.05). The percentage of SDC changes was down to -11.7 +/- 5.4%. Phase 4 (digoxin taken 2 hours before bisacodyl) showed an increase in SDC in comparison with phase 3 (digoxin alone) but was not statistically significant (0.65 +/- 0.03 vs. 0.62 +/- 0.03 ng/ml, M +/- SE, p greater than 0.05). The average frequency of diarrhea was 3.5 times in the first day of phase 2 and 2.7 times in the first day of phase 4. We conclude that in volunteers bisacodyl interacts with digoxin resulting in reduction of the SDC. Interference of the absorption is the most likely mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

An epidemiological study of digoxin prescribing in general practice.

The epidemiology of prescribing long-term digoxin was studied in 241 patients from six group general practices. Each patient was assessed for the initial reason for prescribing digoxin and present clinical status, and the serum digoxin concentration was measured between six and 12 hours after the previous dose.The results show that digoxin was most commonly prescribed for elderly patients; 90% of patients were aged 60 years or more. The reasons for prescribing digoxin were considered adequate in only 55% of the total group; 71% of the patients were judged to be clinically well and 75% of the 95 patients with atrial fibrillation had ventricular rates of less than 90 beats per minute. ;Therapeutic' serum digoxin concentrations (0.8-2.0 ng ml(-1)) were observed in only 48% of patients; the level was sub-therapeutic in 46% and potentially toxic in 6%. No clear-cut relationship was found between clinical well-being and serum digoxin concentration. The type of supervision (whether hospital or general practice) did not affect appropriateness of prescribing, clinical well-being or likelihood of achieving a therapeutic serum digoxin level.This study would suggest the need for critical review of digoxin therapy in all patients who are taking it long-term. In some patients its continuance would appear unnecessary; in others, efficacy may be improved either by dose adjustment or by ensuring compliance. On occasions, particularly in patients with sinus rhythm, measurement of serum digoxin concentrations may prove helpful in this evaluation.

Adult↗
PubMed1986

Digoxin prophylaxis following coronary artery bypass surgery.

The effect of the postoperative administration of digoxin to patients undergoing coronary artery bypass surgery on the incidence of supraventricular arrhythmias was studied. Patients were randomly assigned to a control group (n = 51) or digoxin group (n = 47) on a prospective basis. Patient characteristics were similar in both groups, and no patients were receiving digoxin therapy preoperatively or other antiarrhythmic medications. All patients had normal systolic ejection fractions, renal function, and hepatic function. Eight patients (16%) in the control group developed postoperative arrhythmias while seven patients (15%) in the digoxin group developed supraventricular arrhythmias. This difference was not significant. Two patients in the digoxin group developed digoxin-induced arrhythmias, and two other patients experienced digoxin-related nausea and vomiting, which were resolved with discontinuation of the drug. The postoperative administration of digoxin to patients undergoing coronary artery bypass surgery had no effect on the incidence of supraventricular arrhythmias. The prophylactic use of digoxin therapy in this patient population is not recommended unless there is a history of arrhythmias responsive to digoxin therapy.

Adult↗
PubMed1985

Postmortem redistribution of digoxin in rats.

Adult male Wistar rats were treated with either 0.1 or 3 mg/kg body weight X day of digoxin for five days, then killed and stored at 4 degrees C for 12 h in an attempt to mimic the normal preautopsy procedures in our hospital. In rats treated with 0.1 mg/kg body weight X day, the antemortem serum digoxin concentrations (SDC) were 1.1 +/- 0.4 ng/mL while the 12-h postmortem concentration was markedly increased (16.3 +/- 5.9 ng/mL) (P less than 0.01). In rats treated with 3 mg/kg body weight X day, SDC was not changed significantly (11.2 +/- 4.8 ng/mL antemortem and 13.3 +/- 6 ng/mL postmortem). Postmortem redistribution of digoxin was assessed by injection of 125I-labelled digoxin with or without pretreatment with the unlabelled drug. The results indicate that after death passive redistribution of digoxin may take place. When the SDC are within the therapeutic or low toxic range, digoxin may reenter the blood. High antemortem serum concentrations of digoxin may prevent such passive redistribution. Therefore, antemortem digoxin intoxication cannot be reliably inferred on the basis of high postmortem levels of the drug. Digoxin intoxication can be ruled out when postmortem SDC remain within the therapeutic range. The above changes cast doubt on some of the forensic and cardiologic literature, which has in the past been based on incorrect assumptions concerning postmortem behavior of digoxin.

Animals↗
PubMed1985

Brain, myocardium and plasma concentrations and toxicity of digoxin in newborn and adult rats.

Digoxin tissue concentrations and elimination kinetics were determined to explore possible explanations of the age-related changes in response to digoxin in the rat. Digoxin concentrations were measured in brain, myocardium, and plasma of newborn and adult rats at serial time intervals after nontoxic doses and at the time of death after toxiequivalent doses. After SC administration of a nonlethal dose of 500 micrograms/kg digoxin, brain, myocardium and plasma concentrations and areas under the curve of digoxin concentrations vs time were considerably greater (P less than 0.01) in the newborn than in the adult rats. Following toxiequivalent doses of digoxin (2.5X LD50), digoxin concentrations were several fold greater in the myocardium and plasma of adult rats than in newborn specimens; in contrast, despite the 30-fold smaller digoxin dose per kilogram body weight given to 1-day-old rats, mean digoxin concentration was 2.9 times greater in their brain than in adult brain. These findings suggest that changes in tissue distribution and in the disposition of digoxin play a role in the greater sensitivity of newborn rats to digitoxicity and in the distinct digitoxic arrhythmic effects observed in the newborn as compared to the adult rat.

Aging↗
PubMed1979

[Pharmacodynamic studies in suicidal digoxin poisoning (author's transl)].

In two patients with suicidal digoxin poisoning the correlations between serum digoxin concentration and changes in the duration of QTc and the flattening of the T-waves were studied. The digoxin serum half-life following suicidal digoxin poisoning was in the first patient (10 mg beta-acetyl derivative of digoxin) 77 h, prolonged cause of renal insufficiency, and in the second patient 39.6 h. (20 mg beta-acetyl derivative of digoxin). In both patients the digoxin induced flattening of the T-wave reached a plateau of maximum efficacy at a serum level of 2-3 ng/ml with no further change up to a serum level of 13.2 ng/ml and 9.6 ng/ml respectively. A linear correlation, however, was found between the digoxin serum concentration and the digoxin induced shortening of QTc, r = 0.88 and r = 0.92 respectively. A plateau maximum efficacy was not found. The regression equations were y = -12.0 chi + 430.8 and y = -8.0 chi + 391.9 respectively. The shortening of QTc is therefore an important parameter for the diagnosis of digoxin poisoning. It can be determined very quick with no methodical problems.

Digoxin↗
PubMed1977

The effect of oral spironolactone and intravenous canrenoate-K on the digoxin radioimmunoassay.

Twenty patients receiving a constant maintenance therapy of digoxin preparations were selected, and daily plasma digoxin concentrations were measured using the clinical assays gammacoat 125I-digoxin radioimmunoassay. A single intravenous dose of canrenoate-K was given to 10 patients, thus producing after 5 min. a rapid rise of plasma digoxin concentrations, which varied from 121.1 to 214.3% of the baseline value (100%). In 3 of these patients, plasma digoxin concentrations were measured serially over a period of 8 hrs. and yielded digoxin levels of 81.5, 112.5 and 122.5% of the baseline value. The other 10 patients received an oral dose of 100 mg spironolactone twice a day, and plasma digoxin determinations were carried out daily. Up to the fifth day, a continuous rise of average digoxin levels was found (on day 5, 181.0%) as long as digoxin and spironolactone were continued. From the sixth to the ninth day of therapy, average mean values remained fairly constant (on days 6-9, 168.9, 173.6, 170.8, 172.5% respectively). Contradictory results have been obtained when the interference of spironolactone, canrenone or canrenoate-K on the radioimmunoassay was studied [1, 2]. This study is a further contribution for evaluating the specifity a commercially available 125J-labeled digoxin kit.

Canrenoic Acid↗
PubMedDate not supplied

Digoxin pharmacokinetics and dosage requirements in pediatric patients.

The pharmacokinetic properties and dosage guidelines for digoxin in pediatric patients with congestive heart failure are reviewed. Interindividual variability in the pharmacokinetics of digoxin in pediatric patients has been reported. The bioavailability of digoxin elixir in newborns and infants is similar to adults; however, the apparent volume of distribution has been reported to be greater in infants than in adults. The total body clearance of digoxin is lowest in premature and full-term neonates and highest in infants aged one month to one year. The elimination half-life of digoxin has been reported to vary significantly among the different age groups of pediatric patients. The usefulness of monitoring digoxin serum concentrations in pediatric patients remains a controversial issue. Serum samples should be drawn under steady-state conditions to evaluate predicted daily maintenance doses. Although infants have been reported to be more tolerant than adults to elevated serum digoxin concentrations, infants experience a higher rate of digoxin toxicity than previously realized. Recent studies have shown appropriate therapeutic response in neonates and infants when low dosages of digoxin are administered. Low digoxin dosage regimens should be used initially for infants with congestive heart failure. If the clinical response is unsatisfactory or if toxicity is suspected, steady-state serum concentrations should be determined and the dosage adjusted.

Adolescent↗
PubMed1983

Digoxin toxicity and electrolytes: a correlative study.

Serum levels of sodium, potassium, calcium, magnesium and digoxin were studied in 67 patients on maintenance dose of digoxin, 42 with digitoxicity and 25 without. The mean serum digoxin level of toxic group was significantly higher (p less than 0.001) than non-toxic group. The mean serum potassium was significantly lower in toxic group (p less than 0.05) as compared to the non-toxic group. Of the toxic patients, 23.8% had hypokalemia. Hypokalemia resulted by significantly higher (p less than 0.005) dose of diuretic used in toxic group. The mean serum digoxin level of hypokalemic toxic group was significantly lower as compared to the normokalemic toxic group (p less than 0.001) and it was interesting to note that all hypokalemic toxic patients had their serum digoxin levels below 3 ng/ml (3.84 n mol/ml) and well within therapeutic range. There was a positive correlation between serum digoxin and potassium level amongst toxic patients (p less than 0.001). Thus, in patients on maintenance dose of digoxin therapy, use of large dosage of diuretics may result in hypokalemia, causing digitalis toxicity even at low serum digoxin levels. Serum digoxin level alone may fail as an independent guide in diagnosis of digoxin toxicity in presence of hypokalemia.

Adult↗
PubMed1983

[Radionuclide methods of determining digoxin levels].

The digoxin level in the blood was determined in 92 patients with blood circulatory insufficiency using radioimmunoassays (Sea Ire-Sorin kits) and radionuclide (86 Rb) methods. Pharmacokinetics of digoxin was evaluated on the basis of a two-compartmental mathematical model (by J. Y. Wagner). Direct correlation between the value of a maintenance dose and digoxin concentration in the blood was established. Digoxin values in the blood determined by the radionuclide method, were somewhat higher than the indices of the radioimmunological method. According to this method digoxin therapeutic concentrations in the blood were: 0.4-2.8 ng/ml; according to the radionuclide method 0.6-4.8 ng/ml. Symptoms of digoxin intoxication (overdosage) in rising its concentration in the blood up to 1.1-3.3 ng/ml by the radioimmunoassay and up to 2.2-6.1 ng/ml by the radionuclide method were recorded. It can be accounted for by the fact that bigger values of digoxin active metabolites are determined by the radionuclide method, whereas the radioimmunoassay is more specific to digoxin. Pharmacokinetic parameters (distribution volume, digoxin clearance, the period of semi-elimination) calculated by two methods, brought about the same results. Regularities of the changes of digoxin pharmacokinetics in patients with disturbed renal function are analysed.

Digoxin↗