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PubMed1999

Suppression of total digoxin concentrations by digoxin-like immunoreactive substances in the MEIA digoxin assay. Elimination of negative interference by monitoring free digoxin concentrations.

Digoxin-like immunoreactive substances (DLIS) cross-react with antidigoxin antibody and falsely elevate immunoassay-measured total digoxin concentrations. The fluorescence polarization immunoassay (FPIA) for digoxin showed high cross-reactivity with DLIS, but a new microparticle enzyme immunoassay (MEIA) had low cross-reactivity. The concentration of digoxin in the presence of DLIS was falsely lowered (negative interference) when measured by MEIA. We prepared the following serum pools: 2 normal (no DLIS), 2 from patients with uremia, and 3 from patients with liver disease (high DLIS). No patients received digoxin or digitoxin. When normal pools were supplemented with known concentrations of digoxin, total and free concentrations measured by both assays were comparable, but when liver and uremic pools containing high DLIS were supplemented with digoxin, the measured total digoxin concentrations were lower by MEIA and higher by FPIA. However, by taking advantage of 25% protein binding of digoxin and high protein binding of DLIS, free digoxin levels were not affected by DLIS. In 2 patients receiving digoxin but without volume expansion, total and free digoxin concentrations measured by both assays were comparable; in the 2 volume-expanded patients, only free digoxin concentrations were comparable. Monitoring free digoxin concentration can eliminate negative interference of DLIS in the MEIA for digoxin.

Cross Reactions↗

PubMed1992

Digoxin and digoxin derivative induced arrhythmias: in vitro binding and in vivo abolition of arrhythmias by digoxin immune Fab (DIGIBAND).

OBJECTIVE: The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides. METHODS: The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated. RESULTS: In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents. CONCLUSIONS: Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo.

Acetyldigoxins↗

PubMed1985

Tissue digoxin concentrations and digoxin effect during the quinidine-digoxin interaction.

Quinidine elevates serum digoxin concentration in part by reducing the volume of distribution of digoxin, which implies that quinidine displaces digoxin from tissues. The purposes of this study were to: 1) measure the effect of quinidine on tissue digoxin concentrations, and 2) determine if quinidine alters the relation between myocardial digoxin concentration and digoxin effect on myocardial monovalent cation transport. Eighteen dogs were treated with tritiated digoxin until the steady-state serum digoxin concentration was between 1.0 and 1.5 ng/ml. All dogs continued receiving the same dose of digoxin while nine dogs were given quinidine as well. Quinidine was continued until the serum digoxin concentration had increased by at least 25%. At the end of treatment, the serum digoxin concentration in dogs treated with digoxin was 1.2 +/- 0.1 ng/ml compared with 2.1 +/- 0.5 ng/ml in dogs treated with digoxin and quinidine in combination (p less than 0.001). Digoxin concentration in myocardium, skeletal muscle, liver, kidney, stellate ganglion, vagus nerve, femoral nerve, brain and brainstem medulla was higher in dogs treated with a combination of digoxin and quinidine than in dogs treated with digoxin alone, but remained proportional to the serum digoxin concentration in all tissues except the brainstem medulla. Myocardial monovalent cation transport was measured using rubidium-86. The effect of digoxin on myocardial monovalent cation transport did not increase as the serum and myocardial digoxin concentrations increased after quinidine administration.

Animals↗

PubMed2004

Interference of endogenous digoxin-like immunoreactive factors in serum digoxin measurement is minimized in a new turbidimetric digoxin immunoassay on ADVIA 1650 analyzer.

Endogenous digoxin-like immunoreactive factors (DLIF) cross-react with antidigoxin antibody and falsely elevate or lower measured serum digoxin concentrations, depending on the assay design. Recently, Bayer Diagnostics released a turbidimetric assay for digoxin on the ADVIA 1650 analyzer. We studied potential interference of DLIF with this new digoxin assay. We analyzed 40 serum specimens from patients who have pathologic conditions that may increase serum DLIF concentrations. These patients were never exposed to digoxin or other agents that may lead to a measurable digoxin concentration. We also analyzed five specimens from autopsy and five specimens from neonates. Apparent digoxin concentrations were measured using the new turbidimetric digoxin assay, the fluorescence polarization immunoassay (FPIA, Abbott Laboratories, Abbott Park, IL), and also the chemiluminescent immunoassay (CLIA, Bayer Diagnostics). We observed measurable apparent digoxin levels with the FPIA in 5 uremic patients (range 0.24-0.86 ng/mL), 6 patients with liver disease (range 0.21-0.72 ng/mL), in 3 patients in the third trimester of pregnancy (0.21-26 ng/mL), and in 3 neonates (range 0.21-0.46 ng/mL). Four out of 5 autopsy specimens showed measurable apparent digoxin concentrations (0.23-0.81 ng/mL). In contrast, only 1 specimen (a uremic patient) showed an apparent digoxin concentration of 0.26 ng/mL with the turbidimetric digoxin immunoassay (FPIA value 0.86 ng/mL, CLIA value 0.32 ng/mL). Because DLIF is absent in the protein-free ultrafiltrate, we also measured free digoxin concentrations in DLIF-positive patients to ensure that the apparent digoxin concentrations were caused by DLIF. We observed no apparent digoxin concentrations in the protein-free ultrafiltrate in any DLIF-positive specimens. When serum specimens containing elevated concentrations of DLIF but no digoxin were supplemented with a known concentration of digoxin, we observed falsely elevated digoxin concentrations by the FPIA, as expected. In contrast, we observed a good agreement between the target and observed concentrations when the new turbidimetric assay was used. We conclude that DLIF has minimal effect on serum digoxin measurements by the new turbidimetric assay.

Adult↗

PubMed2002

Bidirectional (positive/negative) interference of spironolactone, canrenone, and potassium canrenoate on serum digoxin measurement: elimination of interference by measuring free digoxin or using a chemiluminescent assay for digoxin.

Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with digoxin in clinical practice. Spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for digoxin, and can falsely elevate serum digoxin concentrations. Serum digoxin concentrations were falsely lowered when the microparticle enzyme immunoassay (MEIA) was used. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin activities were measured. We observed digoxin-like activities in the FPIA, but observed no activity with the MEIA or the chemiluminescent assay (CLIA). However, when serum digoxin pools prepared from patients receiving digoxin were supplemented with these compounds, we observed suppression of total digoxin levels with the MEIA. In contrast, no interference was observed in the presence of these compounds when CLIA was used for digoxin measurement. These compounds are strongly protein-bound, and no apparent digoxin activity was observed in the protein-free ultrafiltrate when drug-free sera were spiked with high levels of these compounds. Taking advantage of strong protein binding of these compounds and weak protein binding of digoxin (25%), interference of spironolactone, canrenone, and potassium canrenoate in FPIA and MEIA digoxin assays can be mostly eliminated by monitoring free digoxin concentration. Another approach to avoid this interference is to use the CLIA digoxin assay.

Canrenoic Acid↗

PubMed2002

Effect of Chinese medicines Chan Su and Danshen on EMIT 2000 and Randox digoxin immunoassays: wide variation in digoxin-like immunoreactivity and magnitude of interference in digoxin measurement by different brands of the same product.

Chan Su is a Chinese medicine prepared from the skin gland of a Chinese toad and is used in treating arrhythmia and other heart diseases. Danshen is prepared from the Chinese medicinal plant and is used for various cardiovascular diseases including angina pectoris. The authors studied the potential interference of such medicines with the widely used EMIT 2000 (Dade Behring; Deerpark, IL) digoxin assay and the recently marketed Randox digoxin assay (Randox Laboratories Ltd, Antrim, United Kingdom) (both run on the Bayer ADVIA 1650 analyzer) (Bayer Diagnostics, Tarrytown, NY) and compared their results with an FPIA (Abbott Laboratories) and a chemiluminescent immunoassay (CLIA; Bayer Diagnostics) for digoxin. Aliquots of drug-free serum were supplemented with 1 microL ethyl acetate extract of Danshen or aqueous extract of Chan Su, and apparent digoxin concentrations were measured by all four digoxin immunoassays (FPIA, EMIT, Randox, CLIA). The authors also supplemented aliquots of several different serum pools prepared from patients taking digoxin with very small amounts of Chan Su or Danshen extract and compared digoxin values with the control digoxin values (serum pool containing no Chinese medicine). The authors observed no interference of Danshen in either EMIT, Randox, or CLIA assay but observed an interference with the FPIA assay. On the other hand, the authors observed high interference of Chan Su in the FPIA assay but moderate interference with the EMIT 2000 and Randox digoxin assays. CLIA assay was again free from any interference. The authors also observed a wide variation in digoxin-like immunoreactivity and magnitude of interference in digoxin immunoassay in different brands of Chan Su and Danshen, indicating poor quality control in manufacturing of these Chinese medicines. Taking advantage of the high protein binding of digoxin-like immunoreactive components of Chan Su, the authors further demonstrated that interference of Chan Su in EMIT 2000 and Randox assays can be mostly eliminated by monitoring free digoxin.

Bufanolides↗

PubMed1980

[Digoxin therapy in patients with long-term digitalis therapy. Comparison of the digoxin blood level after oral administration of digoxin and beta-methyldigoxin].

UNLABELLED: The serum digoxin levels of 23 patients were measured by radio immune assay. The patients were divided into 2 groups receiving either 0,5 mg digoxin b.i.d. or 0,25 mg digoxin b.i.d. orally after having been changed from a maintenance dose of 0,2 mg beta-methyl-digoxin b.i.d. The applicated digoxin was the preparation Lenoxin. The question was whether typical or reduced maintenance doses of digoxin in the new preparation reached therapeutic digoxin serum levels in the absence of renal insufficiency. RESULTS: 1. The maintenance dose of 0,2 mg beta-methyl-digoxin produced stable serum digoxin levels within non-toxic range in all patients; 2. the dosage of 0,5 mg digoxin (group 1) induced accumulation to toxic levels (2,14 mg/ml). A change to 0,25 mg digoxin led to therapeutical serum levels; 3. when using the dosage of 0,25 mg digoxin from the onset of the test (group 2) accumulation was avoided and normal serum digoxin levels were observed during the test period.

Administration, Oral↗

PubMed1992

Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies.

Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration-time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy.

Adult↗

PubMed1990

Monitoring free digoxin instead of total digoxin in patients with congestive heart failure and high concentrations of digoxin-like immunoreactive substances.

Digoxin-like immunoreactive substances (DLIS) are present in patients with conditions associated with volume expansion (including hypervolemic hypertension, renal failure, and liver failure) and in pre-eclampsia and premature birth. These strongly-protein-bound substances cross-react with anti-digoxin antibodies and cause falsely increased measured concentrations of digoxin in serum. Patients with congestive heart failure (CHF) often have volume expansion and are receiving digoxin therapy. They are also very sensitive to digoxin toxicity and have a very narrow therapeutic range (1.0-1.9 nmol/L). We found monitoring the concentrations of free digoxin (in protein-free ultrafiltrates) helpful in eliminating the interferences of DLIS in CHF patients. DLIS concentrations were measured by fluorescence polarization assay. Concentrations of DLIS were detectable in significantly more (58.3%) of the 12 CHF patients (group A) who were not receiving digoxin than in the 22 normal volunteers tested (13.6%) (P less than 0.05 by both chi-square and Fisher's exact test). Protein-free filtrates from patients or normal volunteers did not show any measurable DLIS activities. We also determined the concentrations of total and free digoxin in 12 patients with CHF who were receiving digoxin (group B) and compared the results with those for 22 patients receiving digoxin without the diagnosis of CHF or any known pathological conditions that could increase DLIS concentrations. The ratio of free to total digoxin in patients in group B was significantly lower (mean = 52.8%, SD 10.2%) than in those receiving digoxin (mean = 72.7%, SD 6.5%) for other reasons (independent two-tailed t-test, P less than 0.05).

Digoxin↗

PubMed1996

Estimating concentrations of total digoxin and digoxin-like immunoreactive substances in volume-expanded patients being treated with digoxin.

High concentrations of digoxin-like immunoreactive substances (DLIS) artificially increase serum digoxin concentrations. However, DLIS are absent in the protein-free ultrafiltrate because of their strong binding with serum macromolecules, whereas approximately 75% of digoxin can be found in the ultrafiltrate. Using regression analysis, we devised equations by which total digoxin concentration can be calculated from free digoxin and albumin concentrations in serum. We used two different assays, fluorescence polarization and chemiluminescence, for measuring total and free-digoxin concentrations in sera. Both equations were very similar. Because measured concentrations of digoxin in the serum exhibit DLIS interferences, the measured concentrations were sometimes higher in volume-expanded patients than the calculated digoxin concentrations. We also estimated the extent of interferences from DLIS by subtracting the calculated digoxin concentration from the measured digoxin concentration in volume-expanded patients.

Cardenolides↗

PubMed1989

Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity.

Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF.

Aged↗

PubMed2000

Positive and negative interference of the Chinese medicine Chan Su in serum digoxin measurement. Elimination of interference by using a monoclonal chemiluminescent digoxin assay or monitoring free digoxin concentration.

An over-the-counter Chinese medicine, Chan Su, is used as a cardiotonic agent. We demonstrated significant digoxin-like immunoreactivity in various organic and aqueous extracts of Chan Su. For example, when a 20-microL aliquot of an aqueous extract of Chan Su powder (1 mg/mL) was added to a 2-mL aliquot of a drug-free serum, the observed digoxin-like immunoreactivity was 2.76 ng/mL (3.53 nmol/L) digoxin equivalent using the fluorescence polarization immunoassay (FPIA). The magnitude of interference was much lower (0.94 ng/mL [1.20 nmol/L]) with the microparticle enzyme immunoassay (MEIA), and no interference was observed with the chemiluminescent assay (CLIA). We also observed a significant positive interference of the extract with the serum digoxin measurement using FPIA. In contrast, we observed a negative interference (falsely lowered digoxin concentration) of the extract in the serum digoxin measurement with the MEIA. The extract had no effect on the serum digoxin measurement with the CLIA. By taking advantage of the high protein binding of Chan Su and only 25% protein binding of digoxin, we further demonstrated that positive interference of Chan Su in the FPIA and negative interference of Chan Su in the MEIA of digoxin could be eliminated by monitoring the free digoxin concentration.

Amphibian Venoms↗

PubMed2003

Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Significant variation in digoxin-like immunoreactivity among commercial ginsengs.

Asian and Siberian ginsengs contain glycosides with structural similarities to digoxin. We studied potential interference of ginseng in 5 digoxin immunoassays in 3 Asian (2 liquid extracts, 1 capsule) and 3 Siberian ginseng preparations (1 liquid extract, 2 capsules). With the fluorescence polarization immunoassay (FPIA), we observed apparent digoxin activity in 1 Asian liquid preparation and in the liquid extract and 1 capsule form of Siberian ginseng. In mice fed ginseng, we observed digoxin activities in the serum (Asian, 0.48-0.68 ng/mL [0.6-0.9 nmol/L]; Siberian, 0.20-0.47 ng/mL [0.3-0.6 nmol/L]), indicating that such interferences also occur in vivo. Serum pools prepared from samples from patients receiving digoxin and then supplemented with Asian or Siberian ginseng showed falsely increased digoxin values using the FPIA (e.g., for Asian ginseng, 1.54 ng/mL [2.0 nmol/L] vs control value, 1.10 ng/mL [1.4 nmol/L]) and falsely decreased values using the microparticle enzyme immunoassay (MEIA; 0.73 ng/mL [0.9 nmol/L] vs control value, 1.04 ng/mL [1.3 nmol/L]). Digoxin-like immunoreactive substances (DLISs) showed synergistic effects with ginsengs in interfering with the FPIA and MEIA for digoxin. No interference was observed with 3 other digoxin assays, even in the presence of elevated DLISs.

Animals↗

PubMed1978

Monitoring digoxin therapy. The use of plasma digoxin concentration measurements in the diagnosis of digoxin toxicity.

The usefulness of measuring plasma digoxin concentrations in the diagnosis of digoxin toxicity has been assessed in 83 in-patients. The mean plasma digoxin concentration in clinically toxic patients was significantly higher than the mean concentration in non-toxic patients. The overlap between the groups, however, was extensive and could partly be accounted for by hypokalaemia in those toxic patients whose plasma digoxin concentration was less than 3 ng/ml. There was, in addition, a higher incidence of hyperkalaemia, without obvious cause, in toxic patients than in non-toxic patients. Consideration of the incidence of various non-cardiac factors, specifically plasma potassium concentration greater than 5.0 mmol/l, plasma creatinine concentration greater than 150 mumol/l, daily maintenance dose greater than 6 microgram/kg, and age greater than 60 years, led to the development of guidelines to aid in the diagnosis of digoxin toxicity. Patients with plasma digoxin concentration greater than 3 ng/ml or with hypokalaemia should be considered probably toxic and those with plasma digoxin concentration greater than or equal to 3 ng/ml in the absence of hypokalaemia should only be considered toxic if they have at least two of the non-cardiac factors outlined above. Plasma digoxin concentrations could not be predicted with more than 31 per cent certainty by considering the magnitude of those non-cardiac factors.

Aged↗

PubMed1986

Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication.

17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less.

Adolescent↗

PubMed1995

Assessment of the immunoreactivity of digoxin metabolites and the cross-reactivity with digoxin-like immunoreactive factors in the Roche-TDM ONLINE digoxin assay.

Immunoassays for digoxin measurement have long had the problem of low specificity. Antisera used in these assays may not only measure digoxin and the active metabolites but also cross-react with the noncardioactive metabolites and digoxin-like immunoreactive factors (DLIFs). In this study, we describe the analytical performance of the newly introduced Roche-TDM ONLINE digoxin assay on the COBAS FARA II centrifugal analyzer. The assay possessed linearity up to 5.0 ng/ml, sensitivity of 0.19 ng/ml, average recovery of 100.4%, and day-to-day variability of < 6%. The assay demonstrated no cross-reactivity with DLIFs or spironolactone and its metabolites and negligible reactivity with the digoxin noncardioactive metabolites. In addition, the immunoreactivity of the digoxin active metabolites reflected their cardioactivity. We conclude that the Roche-TDM ONLINE digoxin assay is highly specific and precise and suitable for the therapeutic monitoring of this drug.

Antibodies, Monoclonal↗

PubMed2001

Studies on digoxin--14C-acetate incorporation in to digoxin and degenerative changes in the brain in rats administered digoxin.

The human hypothalamus produces an endogenous membrane Na+-K+ ATPase inhibitor digoxin. Digoxin is a steroidal glycoside and could be synthesised by the isoprenoid pathway. The other metabolites of the isoprenoid pathway are cholesterol, dolichol and ubiquinone. We have tried to find out the extent of incorporation of 14C acetate into digoxin in rat brain. The effects of digoxin administration on the rat brain was also studied. The results show that the percentage incorporation of 14C acetate into digoxin is low but detectable. The maximum incorporation was observed for cholesterol, followed by dolichol and finally ubiquinone. The histopathological changes observed after digoxin administration were focal degeneration of the ganglion cells in the cerebrum and cerebellum. The carbohydrate components of the glycoproteins were reduced and the concentration of serotonin, dopamine, and epinephrine showed a significant increase. The role of digoxin in mediating neuronal cell death is discussed.

Acetates↗

PubMed1983

Cross reactivity of the EMIT digoxin assay with digoxin metabolites, and validation of the method for measurement of urinary digoxin.

In evaluating the EMIT (Syva Co.) digoxin assay, we found no cross reactivity between dihydrodigoxin, the major digoxin metabolite, and the EMIT digoxin antibody from two different lots. However, the antibody does cross react, essentially completely, with the digoxin hydrolysis metabolites digoxigenin, digoxigenin mono-digitoxide, and digoxigenin bis-digitoxide. The EMIT method can be used to measure digoxin in urine diluted at least 50- to 100-fold with digoxin-free human plasma; the inter-assay coefficient of variation of this assay is 6%. In addition, we validated the manual EMIT serum digoxin assay, using external ("TRI-rac") quality controls.

Cross Reactions↗