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 433 records · Page 24Linked to original sources
PubMed2000

[Effect of itraconazole on digoxin clearance in patients with congestive heart failure].

We showed a digoxin-itraconazole interaction in three patients in whom digoxin serum concentrations were increased. Their electrocardiograms revealed arrhythmias such as ventricular premature contraction, atrioventricular block, and ST depression. The elimination half-life of digoxin in case 3 patient who continued itraconazole therapy was 8.4 days, which was estimated by nonlinear least squares method from the serum concentrations of digoxin versus time curve. In order to evaluate the influence of itraconazole on pharmacokinetic parameters of digoxin, we estimated digoxin clearance by the Bayesian method using the population pharmacokinetic parameters in Japanese patients. During the concomitant use of itraconazole and digoxin, the digoxin clearance in all patients decreased to 50.5 +/- 8.8% (mean +/- S.D.) of the clearance without itraconazole. When digoxin and itraconazole are used concomitantly, careful monitoring of digoxin serum concentrations is necessary. Based on our results of digoxin clearance evaluation, the dose of digoxin should be reduced to 50% of original dose after itraconazole is started, and digoxin serum concentration might be controlled at the same level before the concomitant use.

Aged↗
PubMed1984

Amiodarone-digoxin interaction. Clinical and experimental observations.

Twenty-two patients were given amiodarone for refractory cardiac arrhythmias, and pre- and post-amiodarone serum digoxin levels were studied. The interval between pre- and post-amiodarone serum digoxin levels ranged from five days to nine months (mean interval, seven weeks). The mean (+/- SD) pre-amiodarone serum digoxin level was 1.0 +/- 0.4 ng/ml, and the post-amiodarone serum digoxin level was 1.9 +/- 0.8 ng/ml (p less than .001). To develop an animal model for study of the digoxin-amiodarone interaction, 18 pigs were given digoxin for a four-week period. Half of the animals were given amiodarone as well as digoxin for the last two weeks of the study. At the end of the initial two-week period, there was no difference in serum digoxin levels between the two groups. At the end of the second two-week period, the serum digoxin level in the group receiving digoxin alone was 0.6 +/- 0.2 ng/ml, and the serum digoxin level in the group receiving the digoxin and amiodarone was 1.2 +/- 0.6 ng/ml (p less than .01). These data confirm the presence of an amiodarone-digoxin interaction in man and show that the pig is an appropriate model for study of this clinical phenomenon in the animal laboratory.

Adolescent↗
PubMed2000

Rosiglitazone does not affect the steady-state pharmacokinetics of digoxin.

Rosiglitazone is a potent insulin-sensitizing oral hypoglycemic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) nuclear receptor and improves glycemic control in patients with non-insulin-dependent diabetes mellitus. The potential for a drug-drug interaction with oral digoxin was investigated. Subjects received both of the study regimens in a random sequence: digoxin 0.375 mg plus matching placebo for rosiglitazone orally each morning for 14 days or digoxin 0.375 mg plus 8 mg rosiglitazone orally each morning for 14 days. There was a 14-day washout period between sessions. Blood and urine were collected over 24 hours beginning on the morning of day 14 for measurement of digoxin concentrations. An equivalence statistical approach was used, with rosiglitazone considered to have no effect on the pharmacokinetics of digoxin if the 90% confidence interval (CI) for the ratio of digoxin plus rosiglitazone relative to digoxin plus placebo was completely contained within the range (0.80, 1.25) for the primary end points, AUC(0-24), and C24. Digoxin AUC(0-24) and C24 values were similar for digoxin 0.375 mg plus matching placebo (18.5 ng.h/mL and 0.579 ng/mL, respectively) and digoxin 0.375 mg plus rosiglitazone (19.1 ng.h/mL and 0.594 ng/mL, respectively). Point estimates were 1.05 (90% CI: 1.01, 1.10) for AUC(0-24) and 1.04 (90% CI: 0.98, 1.11) for C24. Oral and renal clearance were also similar between regimens. Digoxin alone or in combination with rosiglitazone was safe and well tolerated. The most common adverse experience was headache. Coadministration of digoxin with rosiglitazone had no significant effect on the safety or steady-state pharmacokinetics of digoxin.

Adolescent↗
PubMed1992

Changes in the plasma levels and basic pharmacokinetic parameters of digoxin used in combination with gentamicin, amiodarone and spironolactone.

Digoxin was administered intravenously (0.035 mg/kg b.w.). A prior five-day treatment with gentamicin (100 mg/kg b.w., 10 mg/kg b.w., i.m.), amiodarone (30 mg/kg b.w., s.c.) and spironolactone (10 mg/kg b.w., p.o.) caused elevation of plasma digoxin levels primarily because the alpha half-life was prolonged (t1/2 alpha). In a combined five-day application of digoxin with gentamicin (10 mg/kg b.w., i.m.), and of digoxin with amiodarone, the plasma levels of digoxin rose due to the lengthened beta half-life (t1/2 beta). In administering a combination of digoxin and spironolactone, the plasma digoxin levels dropped, t1/2 alpha decreased and t1/2 beta increased. A 15-day digoxin treatment tested combinations of digoxin, from days eight to 15, with gentamicin (10 mg/kg b.w., i.m.); with amiodarone, or with spironolactone. The digoxin level was elevated with the combinations of digoxin-amiodarone and digoxin-spironolactone: t1/2 alpha was longer in both cases, while t1/2 beta was longer only for the digoxin-amiodarone combination. No changes were found in the creatinine clearance or renal histology of experimental animals after treatment, nor were any deviations found in the values of T3, T4 and TTX.

Amiodarone↗
PubMed1987

Pharmacokinetics and interactions of digoxin with phenobarbital in dogs.

In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested for 2 weeks, were then given phenobarbital (13.2 mg/kg orally) for 14 days, and then were given digoxin again (0.022 mg/kg, IV). Comparing prephenobarbital (control) digoxin half-lives of 42.4 +/- 8.8 hours and postphenobarbital digoxin half-lives of 18.0 +/- 2.2 hours, the half-life was significantly (P less than 0.05) decreased after phenobarbital administration. Clearance was increased by 84%, and the volume of distribution given was decreased by 34%. In a second experiment, 5 dogs were given digoxin (0.022 mg/kg, orally) daily for 11 days, and the digoxin kinetics were evaluated after the last dosing. The dogs were then rested and given phenobarbital (13.2 mg/kg, orally) once daily for 14 days and digoxin (0.022 mg/kg) once daily for 11 days, and the pharmacokinetics of digoxin was determined on the last day of dosing. Significant differences in steady-state serum concentrations and the pharmacokinetics of digoxin were not found between the control and phenobarbital phases of the experiment. Mean (+/- SD) half-lives of digoxin were 29.0 +/- 7.2 hours before phenobarbital treatment (control) and were 34.8 +/- 7.2 hours after phenobarbital treatment. In comparing results of the single-dose experiment vs the oral multiple-dose experiment, dogs had shorter half-lives for digoxin after multiple dosing. Therefore, if phenobarbital and digoxin are to be chronically coadministered orally, an adjustment in the digoxin dose is not necessary.

Animals↗
PubMed1984

[Digoxin-amiodarone interaction].

Digoxin plasma levels and digoxin erythrocytic membrane content have been evaluated in 39 patients treated with digoxin and amiodarone in a fixed dose for more than 3 months. The results were compared with those obtained in a group of patients treated with digoxin alone and matched for age, renal function and digoxin daily dose in micrograms/kg body weight. Digoxin plasma levels and digoxin erythrocytic content were significantly higher in patients treated with amiodarone than in controls, thus confirming the interaction between digoxin and amiodarone. The relation between digoxin plasma levels and digoxin bound to erythrocytic membranes--as a marker of the deep tissue accumulation--was not different in patients treated with digoxin or with digoxin + amiodarone, further indicating that amiodarone may not increase digoxin plasma levels by means of a displacement of the glycoside from tissues. The clinical significance of the interaction is still undefined.

Adult↗
PubMed1981

[The action of oxyfedrine on haemodynamics, inotropism and blood perfusion of the partially ischaemic myocardium after digoxin premedication. Studies on anaesthetized dogs (author's transl)].

The effect exerted on the partially ischaemic heart when administering 0.9 mg/kg L-3-(beta-hydroxy-alpha-methylphenethylamino)-3'-methoxypropiophenone (oxyfedrine, ildamen) approx. 10 min after i.v. application of 0.05 mg/kg digoxin was tested on 20 dogs previously anaesthetized with propiomazine-pentobarbital. The following parameters were studied and subsequently compound with the results of former trials of ours' without digoxin premedication: aortic pressure (ASP, ADP), left-ventricular pressure (LVSP, LVEDP), heart rate (HR), cardiac output (HMV), stroke volume (SV), dp/dtmax, dp/dtmax/IP, t-dp/dtmax, blood flow in the normal and partially ischaemic myocardium, the latter being measured with heat conductance probes and labelled microspheres. ASP and ADP show the same reduction--as compared with the control value--both after the administration of oxyfedrine with and without digoxin premedication. After digoxin premedication oxyfedrine led to a somewhat less marked reduction of LVSP; on premedication with digoxin LVEDP was slightly increased whereas it was reduced after additional administration of oxyfedrine as was also the case without digoxin pretreatment. The increase in HR after oxyfedrine is almost the same as without digoxin pretreatment. Also the increase in HMV and the SV lowering are not influenced by digoxin. By administration of oxyfedrine dp/dtmax is always increased by the same amount, starting from the already increased value after digoxin premedication, which is probably an additive effect. The same applies to the quotient dp/dtmax/IP. After oxyfedrine the time t-dp/dtmax is lowered by the same amount, irrespective of a digoxin premedication. Oxyfedrine does not produce a further increase in the heat conductance values after previous application of digoxin; when measuring the blood flow with labelled microspheres the same result was found, which means that by previous administration of digoxin the circulatory effect of oxyfedrine is obviously inhibited. Summing up one can say that by combining the active principles digoxin and oxyfedrine the function parameters of the heart can be influenced only positively.

Anesthesia↗
PubMed1996

Inhibition of the intestinal digoxin absorption and exsorption by quinidine.

Digoxin-quinidine interaction is well documented in the literature. The mechanism is, however, unknown. Previously, it was shown that quinidine reduced digoxin secretion by inhibiting P-glycoprotein (Pgp) in the renal tubule. Because Pgp is expressed in the small intestine to an extent no less than that in the kidney, the study was designed to investigate the possible effect of quinidine on the absorption and exsorption of digoxin in the rat intestine. Results from the everted sac study using different Pgp inhibitors and inducers support that digoxin is a substrate of Pgp in both jejunum and ileum. Plasma concentration of digoxin after intravenous administration increased 2-fold when 1 mg/hr quinidine was coinfused, whereas the amount that appeared in the intestinal lumen decreased by approximately 40%. In the presence of quinidine, total clearance decreased from 318.0 +/- 19.3 to 167.1 +/- 11.0 ml/hr, whereas intestinal clearance decreased from 28.8 +/- 1.7 to 11.1 +/- 1.6 ml/hr. In a separate study, 3H-labeled digoxin was infused intravenously together with luminal perfusion of unlabeled digoxin in the intestine. The change of 3H-labeled digoxin concentrations in plasma and in the intestinal lumen was similar to those in the exsorption study. However, concentration of unlabeled digoxin in plasma or the intestinal lumen did not alter significantly with the addition of quinidine. The absorption clearance in the control group (N = 6, 6.4 +/- 0.47 ml/hr) was significantly higher than that in the group with quinidine coadministration (N = 6, 4.8 +/- 0.31 ml/hr; p < 0.05). This indicates that quinidine may affect not only the elimination of digoxin, such as renal secretion, but also the absorption/exsorption of digoxin in the gastrointestinal tract. This study suggests that Pgp is involved in the drug interaction between digoxin and quinidine in the small intestine. It is clinically important to understand the effect of quinidine on digoxin absorption for further assessment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1976

Inhibition of digoxin absorption by neomycin.

The effect of the administration of the antibiotic neomycin sulfate on the absorption of digoxin was assessed in crossover studies in normal human volunteers. Doses of neomycin (1 and 3 g) markedly depressed serum digoxin concentrations, the areas under the serum concentration-time curves, and cumulative 6-day urinary digoxin excretion after the oral ingestion of 0.5 mg of the cardiac glycoside in tablet form. Neomycin also prolonged the mean time at which peak serum digoxin levels were attained by 1.7 to 3 hr. The inhibition of digoxin absorption was also seen: (1) when the antibiotic was given 3 or 6 hr before the cardiac glycoside, (2) with digoxin tablets of varying dissolution rate, (3) when digoxin or neomycin solutions were used instead of tablets, and (4) in a patient who had had a total gastrectomy. When neomycin was administered with maintenance doses of digoxin, steady state serum digoxin concentrations were significantly reduced. When neomycin was given after a 9-day period of digitalization, the terminal serum digoxin half-life was not significantly shortened. Single doses of neomycin did not interfere with the extent of absorption of d-xylose. In vitro, neomycin did not affect the movement of digoxin across dialysis membranes, nor did it precipitate digoxin out of human bile or intestinal fluid. Neomycin thus clearly depresses the rate and extent of digoxin absorption in man. The mechanism of this effect remains to be established.

Adult↗
PubMed1995

Digoxin and mortality in survivors of acute myocardial infarction: observations in patients at low and intermediate risk. The SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial.

Controversy surrounds the safety of digoxin use in patients recovering from acute myocardial infarction. Previous observations yielded contradictory conclusions. To determine whether digoxin therapy is associated with increased mortality in patients recovering from acute myocardial infarction, we analyzed data from 1731 survivors of acute myocardial infarction enrolled in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT), from which patients with severe heart failure were excluded. At the time of hospital discharge, 175 patients (10%) were taking digoxin. Mortality over 1 year after infarction was significantly higher in patients treated with digoxin than in patients who were not receiving digoxin [27 of 175 (15%) vs. 60 of 1556 (4%); p < 0.0001]. Digoxin administration was associated with increased mortality in several subsets of patients. Since patients treated with digoxin had baseline characteristics predictive of mortality more frequently than their counterparts, we adjusted for these differences. Multivariate analysis performed by the Cox proportional hazards model identified treatment with digoxin as an independent determinant associated with increased death during the first year after myocardial infarction [relative risk (RR) 2.8; 90% confidence interval (CI) 1.8-4.2]. Subgroup multivariate analysis indicated digoxin as an independent predictor of first year death in 464 patients who developed heart failure during their hospital stay (RR 2.3; 90% CI 1.3-4.0), as well as among 1267 patients who did not (RR 3.4; 90% CI 1.7-6.9). The present study suggests a significant excess mortality associated with digoxin therapy after myocardial infarction. The increased mortality risk may be related to unidentified variables associated with the severity of disease in patients treated with digoxin. However, our findings raise concern that the administration of digoxin may contribute to increased mortality in survivors of acute myocardial infarction.

Acute Disease↗
PubMed1981

Digoxin-induced positive exercise tests: their clinical and prognostic significance.

To evaluate the influence of digoxin on the results of exercise testing and the prognostic significance of digoxin-induced positive exercise tests, 98 healthy men, aged 22 to 70 years, were studied. All had normal initial exercise test results. All took digoxin, 0.25 mg daily, for 14 days, and then performed daily exercise tests until each had a negative test response. Five years after these initial tests, a medical history was obtained from 92 of the 98 subjects, and 76 subjects performed repeat exercise tests. Six subjects were lost to follow-up study. Twenty-five percent of subjects (22 of 98) had a digoxin-induced positive exercise test. There was a direct relation between age and the incidence of digoxin-positive tests. The incidence of digoxin-positive tests in men over age 60 years was 100 percent. By 30 seconds after exercise no subject had greater than 1.9 mm S-T depression. No test remained positive for more than 6 minutes after exercise was discontinued. No test was positive 12 days after digoxin was withdrawn. With logistic regression analysis, it was possible to estimate the probability that a subject would have a digoxin-induced positive test. No subject had had a cardiovascular event at follow-up study, but five subjects had a positive repeat exercise test. Four of these subjects had had a digoxin-positive test initially. It is concluded that (1) useful information can be obtained from exercise studies of patients who receive digoxin, (2) the probability that a positive exercise test is due to digoxin can be estimated, (3) to remove the exercise-induced electrocardiographic effect, the drug should be withdrawn for 12 days, and (4) digoxin may unmask subclinical coronary arterial stenosis.

Adult↗
PubMed1993

Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group.

OBJECTIVES: The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure. BACKGROUND: Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy. METHODS: Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin. RESULTS: Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016). CONCLUSIONS: These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Body Weight↗
PubMed1996

Cellular basis for improved left ventricular pump function after digoxin therapy in experimental left ventricular failure.

OBJECTIVES: The present study examined left ventricular (LV) and myocyte contractile performance and electrophysiologic variables after long-term digoxin treatment in a model of LV failure. BACKGROUND: A fundamental therapeutic agent for patients with chronic LV dysfunction is the cardiac glycoside digoxin. However, whether digoxin has direct effects on myocyte contractile function and electrophysiologic properties in the setting of chronic LV dysfunction remains unexplored. METHODS: Left ventricular and isolated myocyte function and electrophysiologic variables were examined in five control dogs, five dogs after the development of long-term rapid pacing (rapid pacing, 220 beats/min, 4 weeks) and five dogs with rapid pacing given digoxin (0.25 mg/day) during the pacing period (rapid pacing and digoxin). RESULTS: Left ventricular ejection fraction decreased in the dogs with rapid pacing compared with that in control dogs (30 +/- 2% vs. 68 +/- 3%, p < 0.05) and was higher with digoxin than that in the rapid pacing group (38 +/- 3%, p = 0.038). Left ventricular end-diastolic volume increased in the rapid pacing group compared with the control group (84 +/- 6 ml vs. 59 +/- 7 ml, p < 0.05) and remained increased with digoxin (79 +/- 6 ml). Isolated myocyte shortening velocity decreased in the rapid pacing group compared with the control group (37 +/- 1 microns/s vs. 59 +/- 1 microns/s, p < 0.05) and increased with digoxin compared with rapid pacing (46 +/- 1 microns/s, p < 0.05). Action potential maximal upstroke velocity was diminished in the rapid pacing group compared with the control group (135 +/- 6 V/s vs. 163 +/- 9 V/s, p < 0.05) and increased with digoxin compared with rapid pacing (155 +/- 12 V/s, p < 0.05). Action potential duration increased in the rapid pacing group compared with the control group (247 +/- 10 vs. 216 +/- 6 ms, p < 0.05) and decreased with digoxin compared with rapid pacing (219 +/- 12 ms, p < 0.05). CONCLUSIONS: In this model of rapid pacing-induced LV failure, digoxin treatment improved LV pump function, enhanced isolated myocyte contractile performance and normalized myocyte action potential characteristics. This study provides unique evidence to suggest that the cellular basis for improved LV pump function with digoxin treatment in the setting of LV failure has a direct and beneficial effect on myocyte contractile function and electrophysiologic measures.

Action Potentials↗
PubMed1998

Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. PAFIT-3 Investigators. The Propafenone in Atrial Fibrillation Italian Trial.

In recent-onset atrial fibrillation, intravenous propafenone has been shown to effectively restore sinus rhythm, whereas the efficacy of intravenous digoxin has been questioned. We directly compared these 2 drugs and placebo in acute atrial fibrillation. One hundred twenty-three patients with atrial fibrillation lasting <72 hours were randomized to a 10-minute intravenous infusion of either propafenone (2 mg/kg, 41 patients) or digoxin (0.007 mg/kg, 40 patients) or placebo (42 patients). After 1 hour, nonconverted propafenone or digoxin patients were switched to the alternative drug, while nonconverted placebo patients were randomized to either propafenone or digoxin. The observation time ended 1 hour later. By 1 hour, conversion rates were 49% in the propafenone group, 32% in the digoxin group (p = 0.12), and 14% in placebo group (p <0.001 vs propafenone, p = 0.08 vs digoxin). After crossover, digoxin converted 5% of propafenone patients, while propafenone converted 48% of digoxin patients (p <0.05). In the 36 nonconverted placebo patients, sinus rhythm was obtained in 53% of cases with propafenone, and in 5% with digoxin (p < 0.05). Globally, among the 116 patients who received a drug as first treatment, 30 of 60 patients (50%) were converted by propafenone versus 14 of 56 (25%) by digoxin (p <0.01) (odds ratio 2.0, 95% confidence interval 1.19 to 3.36). In nonconverters, the ventricular rate reduction was faster (15 vs 45 minutes) and more prominent (-24% vs -14%) with propafenone than with digoxin. In conclusion, intravenous propafenone terminates atrial fibrillation more effectively than either placebo or intravenous digoxin. In addition, in nonconverted patients, it obtains a more rapid and marked control of the ventricular rate.

Acute Disease↗
PubMed1986

Use of digoxin in infants and children, with specific emphasis on dosage.

The foregoing discussion leads to several general conclusions regarding the use of digoxin in the pediatric patient. First, pharmacokinetic studies indicate that somewhat higher doses are required in the infant to attain the same serum levels as in the adult. Important sources for this difference appear to be more rapid body clearance of digoxin and larger volume of distribution in the infant. Second, higher serum digoxin levels are not indicated on the basis of decreased myocardial uptake of digoxin in the infant. Tissue uptake of digoxin, as indicated by myocardium/serum digoxin ratios, is higher in infants and children than in adults. Third, according to results of animal studies, the inotropic sensitivity to digoxin in the young is probably greater--certainly not less--than in the adult. This is opposite to a commonly held view that the immature heart is less sensitive to cardiac glycosides and therefore requires higher serum levels for a therapeutic effect. Rather, the infant has decreased sensitivity of the conduction system to digitalis toxicity, and healthy myocardium less prone to arrhythmia than the adult. Therefore the infant may tolerate, but does not require, higher serum levels of digoxin. Fourth, high levels of serum digoxin (greater than 2 ng/ml) are not associated with greater inotropic effects in the pediatric patient. The higher dosages of digoxin are, instead, associated with greater frequency of toxic effects, especially in infants receiving concomitant diuretic therapy. Therefore, a digoxin dosage recommendation is presented, that will result in mean serum digoxin levels of 1.1 to 1.7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1986

Digoxin-quinidine interaction in the neonatal dog.

The effects of quinidine on steady state serum and tissue digoxin concentrations in the neonatal dog were studied. To determine the effects of quinidine on serum digoxin concentrations, two groups of neonates were evaluated: Group I (n = 11) was digitalized with 40 micrograms/kg body weight, intramuscularly, and placed on a 10 micrograms/kg per day maintenance dose; Group II (n = 7) was digitalized with 50 micrograms/kg per day, intraperitoneally, and placed on a 20 micrograms/kg per day maintenance dose. After 10 days of digoxin alone, quinidine was coadministered (30 mg/kg per day, intraperitoneally) for 7 days. Serum digoxin concentrations were measured before quinidine and 1, 3 and 7 days after combined digoxin-quinidine therapy. In Group I, the control serum digoxin concentration was 1.38 +/- 0.32 ng/ml and after 7 days of combined therapy it was unchanged (1.39 +/- 0.31 ng/ml). In Group II, the control serum digoxin concentration measured 2.80 +/- 0.49 ng/ml and after 7 days of combined therapy it, too, was unchanged (3.10 +/- 0.65 ng/ml). The effects of combined digoxin-quinidine administration on tissue digoxin concentrations were studied in two other groups of neonates. Group III (n = 6) was given a low maintenance dose of digoxin (10 micrograms/kg per day, intramuscularly) and a full 7 days of coadministered quinidine; in Group IV (n = 6), digoxin was given at a higher dose (20 micrograms/kg per day, intraperitoneally) and a shorter duration of combined digoxin-quinidine therapy (3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

[Quinidine-digoxin interaction (author's transl)].

An additional dose of 500 mg of rapidly absorbed quinidine increased the digoxin concentration in serum after 3-5 hours by up to 46% and prolonged digoxin half life from 50 to 100 hours in six probands who were on chronic quinidine-digoxin medication. These effects were not elicited regularly in persons pretreated with digoxin only. The results show that quinidine both diminishes elimination and produces transient redistribution of digoxin. Chronic quinidine medication leads to protracted digoxin elimination resulting in marked prolongation of digoxin half life. This is the reason for persisting increase of digoxin concentration in serum. Estimation of serum digoxin levels should thus be done 8 hours after the last quinidine (and digoxin) medication at the earliest. On cessation of digoxin, as is done preparing for electric cardioversion, one should remember that digoxin elimination is clearly prolonged should quinidine treatment be continued.

Digoxin↗
PubMed2000

Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein.

OBJECTIVE: Recent data indicated that disposition of oral digoxin is modulated by intestinal P-glycoprotein. The cardioselective beta-blocker talinolol has been described to be secreted by way of P-glycoprotein into the lumen of the gastrointestinal tract after oral and intravenous administration. We therefore hypothesized that coadministration of digoxin and talinolol may lead to a drug-drug interaction based on a competition for intestinal P-glycoprotein. METHODS: Pharmacokinetics of digoxin (0.5 mg orally), talinolol (30 mg intravenously and 100 mg orally), and digoxin plus talinolol orally, as well as digoxin plus talinolol intravenously, were assessed in five male and five female healthy volunteers (age range, 23 to 30 years; body weight, 60 to 95 kg) in a changeover study with at least a 7-day washout period. Digoxin and talinolol were analyzed by fluorescence polarization immunoassay and HPLC, respectively. RESULTS: Oral coadministration of 100 mg talinolol increased the area under the concentration-time curve (AUC) from 0 to 6 hours and the AUC from 0 to 72 hours of digoxin significantly by 18% and 23%, respectively (5.85+/-1.49 versus 7.22+/-1.29 ng x h/mL and 23.0+/-3.3 versus 27.1+/-3.7 ng x h/mL, for both P<.05) and the maximum serum levels by 45%. Renal clearance and half-life of digoxin remained unchanged. Coinfusion of 30 mg talinolol with oral digoxin had no significant effects on digoxin pharmacokinetics. Digoxin did not affect the disposition of talinolol after both oral and intravenous administration. CONCLUSION: We observed a significantly increased bioavailability of digoxin with oral coadministration of talinolol, which is most likely caused by competition for intestinal P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗