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PubMed1987

Digoxin-like immunoreactive substance in fetuses with and without cardiac pathology.

The concentration of digoxin-like immunoreactive substance was measured by immunoassay in umbilical venous blood from six normal and 19 fetuses with a variety of cardiac and noncardiac disorders. Fetal blood was obtained either by percutaneous umbilical blood sampling (n = 13) or at delivery (n = 12). Three women received digoxin for fetal indications. Healthy control fetuses had significantly less digoxin-like immunoreactive substance measured (mean concentration below the limit of the assay sensitivity) than was found in ill fetuses whose mothers received digoxin (p less than 0.005). However, the fetal concentrations of immunoreactive digoxin in fetuses with a cardiac abnormality were similar whether the mother had (0.93 +/- 0.4 ng/ml) or had not (1.27 +/- 0.4 ng/ml) received digoxin (p = 0.1452). Although there was a significant negative correlation between digoxin concentration and gestational age (R = -0.5079, p less than 0.01), the youngest fetuses examined were generally the sickest. The correlation with gestational age was not significant if the normal control fetuses were excluded. One fetus with a cardiac tachyarrhythmia was examined during and after transplacental therapy. There was no change. It is possible that previously measured "digoxin" in "treated" fetuses represents digoxin-like immunoreactive substance and that only small amounts of maternally administered digoxin actually reach the ill fetus. Our findings suggest that a randomized trial of maternal digitalization for the treatment of fetal supraventricular tachycardia is essential prior to its acceptance as effective therapy.

Blood Proteins↗
PubMed1998

Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein.

We present a digoxin-clarithromycin interaction in two patients in whom digoxin concentrations were unexpectedly increased. The ratio of renal digoxin clearance to creatinine clearance in one patient was lower during the concomitant administration of clarithromycin (0.64 and 0.73) than that after cessation of clarithromycin administration (1.30 +/- 0.20; mean +/- SD). Because P-glycoprotein could play an important role in the renal secretion of digoxin, we hypothesized that clarithromycin decreases renal digoxin excretion by inhibiting P-glycoprotein-mediated transport. Digoxin transport was evaluated with use of a kidney epithelial cell line, which expresses the human P-glycoprotein on the apical membrane by transfection with MDR1 complementary deoxyribonucleic acid. Clarithromycin inhibited the transcellular transport of digoxin from the basolateral to the apical side in a concentration-dependent manner and concomitantly increased the cellular accumulation of digoxin. These results suggest that clarithromycin may inhibit the P-glycoprotein-mediated tubular secretion of digoxin, and this interaction mechanism may contribute to an increase in the serum digoxin concentration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

Digoxin toxicity associated with amiodarone therapy in children.

The addition of amiodarone to digoxin therapy in nine children caused a sharp increase in digoxin serum concentrations (68% to 800%) in the presence of preserved serum creatinine and BUN concentrations. Digoxin half-life was prolonged. Digoxin accumulation could be attributed in part to the decrease in the renal clearance of digoxin resulting from inhibited tubular secretion of the drug and to the reduction in the distribution volume of digoxin caused by amiodarone. Creatinine clearance was not affected by amiodarone. This interaction appears to be more acute in children than in adults, presumably because of the more important role of the renal tubular secretion of digoxin in children. Whenever digoxin and amiodarone therapy are combined, the digoxin serum concentration should be monitored carefully, with appropriate reduction of the digoxin dose.

Adolescent↗
PubMed1997

Emergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin.

STUDY OBJECTIVE: To compare the effects of i.v. diltiazem and i.v. digoxin on ventricular rate control in the emergency treatment of acute atrial fibrillation and flutter (AFF). METHODS: This prospective, randomized, open-label trial involved 30 consecutive patients who presented with acute AFF to the emergency department of an urban, 420-bed community teaching hospital from April 1993 through March 1994. Exclusion criteria included systolic blood pressure lower than 100 mm Hg, treatment with calcium-channel blockers other than diltiazem, lack of informed consent, and objection of the private physician. Patients were randomly assigned to receive either i.v. diltiazem alone, i.v. digoxin alone, or both. Heart rate control was defined as a ventricular rate of less than 100 beats/minute. I.v. digoxin, 25 mg, was given as a bolus at time 0 and at time 30 minutes. An initial dose of .25 mg/kg diltiazem was given intravenously over the first 2 minutes, followed by a dose of .35 mg/kg at time 15 minutes and then a titratable i.v. infusion at a rate of 10 to 20 mg/hour to maintain heart rate control. The dosing regimens were the same whether the drugs were given alone or in combination. Heart rhythm, heart rate, and blood pressure were measured at time 0, 5, 10, 15, 30, 60, 120, and 180 minutes. Statistical significance was assessed with the use of Student's t test and ANOVA methodology. RESULTS: At time 0, the heart rate (mean +/- SD) was 150 +/- 19 beats/minute in the diltiazem group and 144 +/- 12 in the digoxin group (difference not significant, P = .432). The decrease in heart rate from time 0 reached statistical significance at time 5 minutes in the diltiazem group (P = .0006); the mean rates at time 5 minutes were 111 +/- 26 beats/minute for diltiazem and 144 +/- 13 for digoxin. The decrease in heart rate achieved with digoxin did not reach statistical significance until time 180 minutes (P = .0099), at which time the rates were 90 +/- 13 for diltiazem and 117 +/- 22 for digoxin. CONCLUSION: Treatment of acute AFF with i.v. diltiazem decreases ventricular heart rate significantly within 5 minutes, compared with 3 hours for treatment with i.v. digoxin. No advantage was noted within 3 hours for i.v. treatment with a combination of diltiazem and digoxin. I.v. diltiazem is superior to i.v. digoxin in the emergency control of ventricular rate in acute AFF and should be considered as a drug of choice for this condition. This study was not large enough to adequately assess adverse effects, and further studies may be warranted for clinical validation.

Acute Disease↗
PubMed2003

Lack of interaction of digoxin and P-glycoprotein inhibitors, quinidine and verapamil in human placenta in vitro.

OBJECTIVE: To determine the effect of quinidine and verapamil, known antiarrhythmic agents and P-glycoprotein (Pgp) inhibitors, on digoxin transport from the maternal to the fetal compartment in the isolated perfused human placenta. STUDY DESIGN: Isolated placental cotyledons from normal human placentae (n=20) were dually perfused with M199 medium enriched with albumin (0.3%) and glucose (0.1%). The maternal and the fetal circulation flow rates were 12 and 6 ml/min, respectively. Closed circulations were used to evaluate steady state transplacental gradient formation. In six placentae quinindine was added to the maternal circuit; after 45 min of perfusion, digoxin was added to the maternal circulation. The effect of verapamil on digoxin transfer from the maternal to the fetal compartments was explored in five placentae. In six additional placentae the transfer of digoxin was studied in the absence of quinidine. Transplacental passage of digoxin was calculated from repeated fetal and maternal perfusate samples. Digoxin levels were determined in perfusate samples by fluorescence polarization immunoassay. Antipyrine was added to the maternal reservoir of all placentae as reference substance. RESULTS: The transfer of digoxin (alone) and in the presence of quinidine or verapamil was 10.93+/-3.71, 9.00+/-5.2 and 12.94+/-4.86%, respectively. The levels of digoxin in the fetal compartment, 0.62+/-0.20, 0.48+/-0.29 and 0.60+/-0.26 ng/ml, respectively, were not significantly affected by quinidine and verapamil. These Pgp modulators, also did not influence significantly the steady state levels of digoxin in the maternal compartment. CONCLUSION: Neither quinidine nor verapamil affected the transplacental transfer of digoxin in vitro in normal human placentae. In contrast to the other tissues, they do not inhibit Pgp activity in term human placentae.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1997

Effects of a lipoxygenase inhibitor on digoxin-induced cardiac arrhythmias in the isolated perfused guinea-pig heart.

1. The effects of a lipoxygenase inhibitor, BW A4C, on digoxin-induced arrhythmias and cardiac dynamics (contractile force, perfusion pressure, heart rate) were investigated in Langendorff-perfused isolated guinea-pig hearts. In the control group, arrhythmias were induced by 25 micrograms/ml digoxin at a perfusion rate of 0.5 ml/min. In the treated groups, BW A4C (1 and 0.3 microM) perfused continuously from 15 min prior to digoxin until cardiac arrest occurred. Digoxin exposure (microgram/g wet weight of heart) for the occurrence of arrhythmias and cardiac arrest were the parameters evaluated to assess cardiotoxicity. 2. Digoxin caused a marked increase in leukotriene B4 release in the coronary effluent, and was collected during tachyarrhythmias. BW A4C markedly inhibited the digoxin-induced elevation of LTB4. 3. BW A4C (1 and 0.3 microM) did not prevent the onset of ventricular fibrillation and ventricular tachycardia despite a slight delay in the occurrence of ventricular fibrillation and cardiac arrest at the 0.3 microM concentration. 4. Contractile force increased significantly after digoxin infusion which was concomitant with the time of onset of arrhythmias. In the presence of BW A4C, the contractile force increased, but not significantly. Perfusion pressure increased initially after digoxin infusion in the absence and the presence of BW A4C, but not significantly. 5. These findings show that the lipoxygenase inhibitor lacked any protective action on digoxin-induced arrhythmias despite its effective suppression of digoxin-induced elevation of LTB4 in coronary effluent.

Animals↗
PubMed2002

Clinical benefits of low serum digoxin concentrations in heart failure.

OBJECTIVES: We sought to determine whether there was a relationship between serum digoxin concentration (SDC), including SDCs typically regarded as low, and clinical efficacy related to digoxin in patients with symptomatic left ventricular dysfunction. BACKGROUND: Digitalis glycosides have been used for 200 years in the treatment of heart failure (HF), but the SDC required for optimal clinical efficacy and acceptable toxicity remains controversial. METHODS: This relationship was investigated by utilizing data from two randomized, double-blinded, placebo-controlled, digoxin-withdrawal trials: the Prospective Randomized study Of Ventricular failure and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin on Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Major end points were worsening HF, change in left ventricular ejection fraction and treadmill time after randomization. The primary analysis investigated the relationship between SDC at randomization and these end points. A secondary categorical analysis compared these end points in patients who discontinued digoxin versus patients who continued digoxin and had low (0.5 to 0.9 ng/ml), moderate (0.9 to 1.2 ng/ml) or high (>1.2 ng/ml) SDCs at randomization. RESULTS: Multiple regression analysis failed to find a relationship between randomization SDC, considered as a continuous variable, and any study end point (all p > 0.236). Multivariable Cox analysis found that the risk of worsening HF was significantly less (all p < 0.02) for patients in any category of SDC who continued digoxin, as compared with patients withdrawn from digoxin. Specifically, patients in the low SDC category were significantly less likely than placebo patients to experience worsening HF during follow-up (p = 0.018). CONCLUSIONS: The beneficial effects of digoxin on common clinical end points in patients with HF were similar, regardless of SDC.

Aged↗
PubMed2001

Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers.

OBJECTIVE: This study was undertaken to determine whether levetiracetam (Keppra) affected the pharmacokinetic or pharmacodynamic profile of digoxin in healthy adults. METHODS: Seven men and four women (19-48 years old) completed this double-blind, placebo-controlled study. Each received digoxin 0.25 mg once daily (0.5 mg on day 1) during the 1-week run-in period, followed by two 1-week periods of coadministration of digoxin with levetiracetam (2000 mg/day) or placebo in a two-way crossover design. The pharmacokinetics of digoxin and levetiracetam were assessed by analysis of blood samples. ECG recordings were taken to monitor effects of levetiracetam on digoxin pharmacodynamics. RESULTS: The ratios of geometric means, using a 90% confidence interval, between coadministration of digoxin with levetiracetam or placebo were 103.96% (99.18%, 108.95%) for AUC(ss), 100.87% (89.52%, 113.66%) for C(max), 97.67% (82.76%, 115.26%) for PTF, and 99.04% (90.98%, 109.00%) for C(min). Although digoxin produced predictable changes in ECG, its pharmacodynamic parameters did not differ significantly between levetiracetam and placebo administration. Furthermore, the pharmacokinetics of levetiracetam were not altered in the presence of digoxin. Co-administration of levetiracetam and digoxin was well tolerated. CONCLUSION: At the doses administered, there was no pharmacokinetic interaction and no evidence of a pharmacodynamic interaction between digoxin and levetiracetam.

Adult↗
PubMed2003

Modulation of digoxin transport across Caco-2 cell monolayers by citrus fruit juices: lime, lemon, grapefruit, and pummelo.

PURPOSE: To evaluate the effects of fresh lime, lemon, grapefruit, and pummelo juices on the transport of digoxin, a P-glycoprotein (P-gp) substrate, in Caco-2 cell monolayers. METHODS: Bidirectional [3H]-digoxin fluxes across confluent Caco-2 cell monolayers were determined in 0-50% fruit juices at pH 7.4. Verapamil HCl (100 microM) served as positive control. Juice toxicity was evaluated by the 3-(4,5 dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. RESULTS: Apical-to-basal (A-to-B) digoxin flux was enhanced by 50% fruit juice in the order of lemon > lime > pummelo > grapefruit. The four fruit juices could be divided into two groups based on their effects on transepithelial electrical resistance (TEER), viability, and digoxin transport activity of the Caco-2 cells. Grapefruit and pummelo juices produced similar digoxin transport profiles that were characteristic of those observed with P-gp inhibitors. Both juices decreased net digoxin efflux by 1.2 U per 10% increase in juice concentration and had a propensity to increase cellular TEER at high concentrations (>30%). However, cellular TEER and viability decreased with increasing concentration of lime and lemon juices. Both juices also produced similar digoxin transport profiles, the A-to-B and B-to-A digoxin Papp increasing with increasing juice concentration above 5%. Net digoxin efflux was 30% of control value and relatively independent of juice concentration. These results paralleled the groupings of the four fruits according to their prominent flavonoid pattern and taxonomy. CONCLUSION: The effects of lime, lemon, grapefruit, and pummelo juices on the TEER, viability, and digoxin transport activity of the Caco-2 cells appeared to be dependent on the dominant flavonoid pattern and taxonomy of the citrus fruits.

Beverages↗
PubMed1982

Digoxin does not alter plasma steroid levels in health men.

Digoxin has been reported to induce feminizing effects in man. It does not compete for estradiol cytosol receptors in human breast carcinoma cells, however, and has no uterotrophic effect. We therefore investigated whether feminization might be due to digoxin action on plasma concentrations of sex steroids. Six healthy men (31.5 +/- 4 yr old) received therapeutic doses of digoxin for 43 days. We measured plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estrone, estradiol, progesterone, 17-hydroxyprogesterone, cortisol, and aldosterone. During 35 days on digoxin levels of these steroids remained in the normal range and there was no change from before-drug values. Digoxin was in the therapeutic range of 1.9 +/- 3 nmol/l throughout. After stimulation by adrenocorticotropic hormone or human choriongonadotropin, the rise in plasma steroids was in the same range as when digoxin was given, as well as 16 wk after it had been discontinued. A normal rise in luteinizing hormone after luteinizing hormone-releasing hormone showed that the hypothalamogonadal feedback was not altered by digoxin. Free testosterone, estradiol, and cortisol concentrations under basal conditions and after stimulation were also the same before and after drug. It is concluded that the estrogen-like activity of digoxin cannot be explained by altered steroid availability from plasma. Feminizing effects attributed to digoxin may be caused by other conditions known to influence sex steroid hormones that are common in patients with heart disease. Our data suggest that digoxin may be the preferred digitalis therapy to avoid feminizing effects.

Adrenal Cortex Hormones↗
PubMed1990

Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.

The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.

Adult↗
PubMed1999

The effect of bosentan on the pharmacokinetics of digoxin in healthy male subjects.

AIMS: To investigate the effect of multiple oral dose treatment with the endothelin receptor antagonist bosentan on the pharmacokinetics of digoxin in healthy subjects. METHODS: This was an open-label, randomized, two-way crossover study in 18 evaluable young male subjects. They received, on two occasions which were separated by at least 2 weeks washout period, 0.375 mg digoxin once daily for 13 days following a loading dose of 0.375 mg given twice on the day before the once daily dosing regimen started. On one occasion treatment with 500 mg bosentan twice daily was started on the eighth day of digoxin treatment and continued for 1 week. Serum concentrations of digoxin were determined up to 24 h postdose on day 8 (first day of bosentan treatment) and day 14 (last day of bosentan treatment) of the digoxin treatment period. Plasma concentrations of bosentan were measured at two time points after the first bosentan dose and up to 12 h after the last morning dose of bosentan. Safety was assessed by adverse events, clinical laboratory tests, blood pressure and pulse rate measurements and ECG recordings. RESULTS: Steady-state of digoxin was always achieved after 7 days of treatment. Serum concentrations of digoxin were within the usual therapeutic range. Average steady-state Cmax and Ctr were 2-2.1 microg l-1 and 0.65-0.69 microg l-1, respectively, when given alone. Bosentan did not lead to statistically significant changes in Cmax and Ctr of digoxin. AUC (0,24h) of digoxin, however, was slightly reduced after 1 week of treatment with bosentan. The reduction was 12% on average with a narrow 95% confidence interval of 0-23%. Bosentan pharmacokinetic parameters after 1 week of treatment were as expected with a mean Cmax of 3260 microg l-1 and a mean AUC (0, 12h) of 12 600 microg l-1 h. CONCLUSIONS: Treatment with bosentan 500 mg twice daily for 1 week did not show clinically relevant effects on the pharmacokinetics of digoxin in healthy human subjects

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine.

AIMS: To assess whether cystatin C, a new serum marker of renal function, is a better index of creatinine or digoxin clearance than serum creatinine in older people. METHODS: Twenty-two volunteers over the age of 65 years (mean 73 +/- 5) were recruited from a healthy elderly volunteer database. None of the volunteers was taking digoxin or other medication known to interfere with digoxin kinetics or assay. Digoxin was infused at a dose of 7-10 microg kg(-1) and blood samples were taken over the following 48 h and assayed for serum digoxin. Serum cystatin C, creatinine and creatinine clearance were measured and a calculated creatinine clearance was estimated using the Cockcroft Gault formula. Digoxin clearance was calculated using a pharmacokinetic software package. All values were log transformed to normalize their distribution. RESULTS: Of the 22 volunteers enrolled into the study, 18 completed the study. Serum cystatin C ranged between 0.72 and 1.89 mg l(-1) and serum creatinine ranged from 69.6 to 153.9 micromol l(-1). Measured creatinine clearance ranged from 38 to 123 ml min(-1) and calculated creatinine clearance from 29.5 to 88.0 ml min(-1). Digoxin clearance ranged from 51.0 to 103.5 ml min(-1). Cystatin C correlated extremely well with creatinine (r=0.93, P<0.001, 95% CI 0.82, 0.97) and with creatinine clearance (r=0.67, P=0.002, 95% CI 0.3, 0.87). Neither serum cystatin C nor serum creatinine correlated with digoxin clearance (r=0.25, P=0.31, 95% CI -0.25, 0.64 and r=0.44, P=0.068, 95% CI -0.03, 0.75, respectively). Measured creatinine clearance, however, did correlate well with digoxin clearance (r=0.55, P=0.018, 95% CI 0.11, 0.81). CONCLUSIONS: Serum cystatin C and serum creatinine show very similar correlations with creatinine and digoxin clearances. Serum cystatin C does not offer any advantages in this respect. It remains to be seen whether cystatin C offers any advantage over creatinine in elderly people in other respects.

Aged↗
PubMed2002

Sex-based differences in the effect of digoxin for the treatment of heart failure.

BACKGROUND: The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated. METHODS: We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables. RESULTS: There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction). CONCLUSIONS: The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function.

Aged↗
PubMed1996

Digoxin transfer across the isolated placenta is influenced by maternal and fetal albumin concentrations.

The aim of this study was to evaluate the influence of different maternal and fetal albumin concentrations on the transplacental transfer and the placental tissue accumulation of digoxin. Digoxin passage across the isolated lobules of 15 human placentae was calculated from repeated fetal and maternal perfusate samples, and placental tissue digoxin concentrations were measured at the end of the experiments. Metildigoxin (Lanitop) was added to the maternal medium at a concentration of 5.70 +/- 0.73 ng mL-1, and maternal and fetal perfusate albumin (BSA) concentrations were kept equal either at a high concentration of 21 g L-1 (Group I; n = 5) or at a low concentration of 3 g L-1 (Group III; n = 5), or differed with a materno-fetal gradient of 21:3 g L-1 (Group II; n = 5). In the experiments with low maternal albumin concentrations (Group III), digoxin concentrations in the maternal circuit decreased to 3.56 ng mL-1, whereas digoxin concentrations in the fetal circuit reached 2.59 ng mL-1 over a 3-h period. With maternal BSA concentrations of 21 g L-1 (Group I and Group II), the decrease in digoxin concentration in the maternal circuit was lower (P < 0.05), and digoxin tissue concentrations at the end of the experiments were smaller (0.45 +/- 0.07 and 0.42 +/- 0.03 v. 0.82 +/- 0.32 ng mg-1 protein, Group I and Group II v. Group III respectively; P < 0.05). Comparing only those lobules with similar high concentrations of maternal protein, fetal BSA concentrations of 21 g L-1 resulted in a greater increase in digoxin concentrations in the fetal circuit (end-feto to initial-maternal digoxin concentrations of 0.44 +/- 0.08 v. 0.37 +/- 0.04 ng mg-1 protein (Group I v. Group II respectively), although this was not significant. The data suggest that maternal and fetal serum albumin concentrations may have an influence on transplacental digoxin transfer, and this should be considered when treating fetuses with cardiac disease transplacentally with glycosides.

Anti-Arrhythmia Agents↗
PubMed1999

Analytical performance of a monoclonal digoxin assay by dry chemistry on the Vitros 950.

Digoxin assay in plasma/serum samples is used for therapeutic measurements as a guide to clinical management of cardiac patients. A thin dry film multilayer monoclonal immunoassay for digoxin, Vitros, was evaluated for analytical performance. The effect of digoxin-like immunoreactive substances (DLIS) was studied assaying plasma samples taken from 100 renal disease patients, 62 hepatic disease patients and 40 pregnant women not receiving digoxin. The Vitros digoxin assay was compared with the AxSym digoxin II assay using plasma samples from 180 patients treated with digoxin. The results revealed satisfactory precision and accuracy for therapeutic drug monitoring purposes: the coefficient of variation (CV%) was lower than 5%; results for dilutions were linear in the range 0.4-3.9 microlg/L and mean analytical recovery was 105%. Measurable DLIS concentrations were observed in 29% of hepatic disease patients and in 7% of renal disease patients with apparent digoxin concentration ranging from 0.4 to 0.75 microg/L. The incidence of DLIS was comparable to that observed with AxSym digoxin II. Comparative results from patient samples gave a regression line equation: Yvitros 950=0.96XAxym +0.14, r=0.89. The data revealed a mean difference of 0.09+/-0.26 microg/L significantly greater than zero (p=0.02). We concluded that Vitros digoxin assay for precision, accuracy and extent of DLIS interference may be a good method for therapeutic drug monitoring; care needs to be taken since assay results generated by Vitros and AxSym analysers are not necessarily interchangeable.

Adult↗
PubMed1987

Receptor radioligand system for measuring digoxin activity.

The purpose of this study was to develop and evaluate a receptor radioligand assay (RRA) for the measurement of digoxin, its metabolites, and endoxin and to compare the results of this assay with those of a fluorescence polarization immunoassay (FPIA) for digoxin. The within-run coefficients of variations for the RRA at digoxin concentrations of 2.0 and 5.0 nmol/L were 21 and 10%, respectively. Serum samples collected from 33 volunteers (not on digoxin medication) measured in the RRA resulted in levels less than 1.23 nmol/L digoxin equivalents (1.23 nmol/L is the lower level of sensitivity for this system). Serum samples collected from 29 patients receiving digoxin for therapeutic purposes and measured in the RRA gave a mean of 3.39 nmol/L digoxin equivalents. The samples collected from the patients receiving digoxin were also measured using FPIA with a mean of 1.75 nmol/L digoxin. The interference of progesterone, 11-alpha-hydroxyprogesterone, cortisone, and six digoxin metabolites on the binding of 3H-ouabain in the RRA was also evaluated.

Animals↗
PubMed1998

Comparison of microparticle enzyme and fluorescence polarization immunoassays in pediatric patients not receiving digoxin.

Previously, investigators have measured endogenous digoxin-like immunoreactive substances (DLIS) in pediatric patients. Digoxin-like immunoreactive substances may cross-react with digoxin assays to produce false-positive digoxin concentrations; hence, the validity of digoxin concentrations in pediatric patients is questionable. The authors compared the presence and magnitude of apparent DLIS using the microparticle enzyme immunoassay (MEIA) AxSYM Digoxin II and the fluorescence polarization immunoassay (FPIA) TDx Digoxin II, in the serum of 80 pediatric patients who were hospitalized with normal serum creatinine but had not been administered digoxin. Patients ranged in age from 1 day to 16 years (mean age, 4.96 +/- 5.17 years). Serum creatinine and total bilirubin were 0.5 +/- 0.18 mg/dl and 1.3 +/- 0.17 mg/dl, respectively. Forty-eight percent of MEIA samples and 79% of FPIA samples had measurable DLIS values. Digoxin-like immunoreactive substance concentrations for the MEIA (0.07 +/- 0.09 ng/ml) and FPIA assays (0.1 +/- 0.1 ng/ml) were statistically different (p = 0.01); however, no sample had a DLIS value >0.38 ng/ml. A poor correlation was noted between patient age, serum creatinine, total bilirubin, and DLIS concentration. The MEIA and FPIA assays effectively minimized DLIS cross-reactivity making both technologies clinically acceptable for serum digoxin measurement in pediatric patients with normal serum creatinine and total bilirubin.

Adolescent↗