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PubMed2003

Role of Na(+), K(+)-ATPase in morphine-induced antinociception.

We evaluated the modulation by Na+,K+-ATPase inhibitors of morphine-induced antinociception in the tail-flick test and [3H]naloxone binding to forebrain membranes. The antinociception induced by morphine (1-32 mg/kg, s.c.) in mice was dose-dependently antagonized by ouabain (1-10 ng/mouse, i.c.v.), which produced a significant shift to the right of the morphine dose-response curve. The i.c.v. administration of three Na+,K+-ATPase inhibitors (ouabain at 0.1-100, digoxin at 1-1000, and digitoxin at 10-10000 ng/mouse) dose-dependently antagonized the antinociceptive effect of morphine (4 mg/kg, s.c.) in mice, with the following order of potency: ouabain > digoxin > digitoxin. This effect cannot be explained by any interaction at opioid receptors, since none of these Na+,K+-ATPase inhibitors displaced [3H]naloxone from its binding sites, whereas naloxone did so in a concentration-dependent manner. The antinociception induced by morphine (5 mg/kg, s.c.) in rats was antagonized by the i.c.v. administration of ouabain at 10 ng/rat, whereas it was not significantly modified by intrathecally administered ouabain (10 and 100 ng/rat). These results suggest that the activation of Na+,K+-ATPase plays a role in the supraspinal, but not spinal, antinociceptive effect of morphine.

Analgesia↗
PubMed1990

Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study.

One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Immunohistochemical studies on the distribution of endogenous digitalis-like substance (EDLS)-containing neurons in the rat hypothalamus, with special consideration on the possibility of their coexistence with posterior lobe hormones.

The distribution of the perikarya of endogenous digitalis-like substance (EDLS)-containing neurons in the rat hypothalamus was studied by immunohistochemistry using digoxin and digitoxin antiserum. In addition, the possible coexistence of EDLS and posterior lobe hormones was examined using an immunohistochemical double-staining technique. Digoxin-like immunoreactive neurons were demonstrated in the paraventricular and supraoptic nuclei and other hypothalamic areas. However, digitoxin-like immunoreactive neurons were not detected in the hypothalamus. A portion of the digoxin-like immunoreactive neurons showed immunoreactivity for vasopressin or oxytocin. From these results, it is suggested that these digoxin-like immunoreactive neurons correspond to "EDLS-producing neurons," and that EDLS seems to act not only as a natriuretic substance but also as a neurohormone or neurotransmitter.

Animals↗
PubMedDate not supplied

Binding and displacement of basic, acidic and neutral drugs in normal and orosomucoid-deficient plasma.

The binding of the basic drugs quinidine, propranolol and amitriptyline, the neutral drug digitoxin and the acidic drug phenytoin to heparinised normal plasma, to orosomucoid (alpha 1-acid glycoprotein)-deficient plasma and to purified orosomucoid and albumin was studied in both the presence and absence of tris (2-butoxyethyl)-phosphate (TBEP) and de-(2-ethylhexyl)-phthalate (DEHP). The addition of TBEP and DEHP to heparinised plasma in concentrations up to 2.5 mmol/L markedly increased the unbound fractions of quinidine and propranolol, but the increase was less for amitiriptyline, TBEP being the most potent displacer. In orosomucoid-deficient plasma, which was prepared by immunoprecipitation, the free fraction of quinidine was similar to that of normal plasma in which maximal displacement with TBEP was obtained. The addition of the displacers to orosomucoid-deficient plasma caused no further reduction in the binding, nor was the plasma binding of digitoxin and phenytoin significantly affected. When combining purified albumin and orosomucoid in concentrations found in normal plasma, quinidine binding approached that of heparinised normal plasma. This study confirms the dominant role of orosomucoid in the variable plasma binding of basic drugs, and underlines the value of using immunologically prepared orosomucoid-deficient plasma and TBEP or DEHP as model displacers.

Amitriptyline↗
PubMed1993

Acute digitalis intoxication--is pacing still appropriate?

Over a six year period, 92 patients intoxicated with either digitoxin or digoxin were admitted to our ICU. Fifty-one patients were treated with cardiac pacing and/or Fab fragments, and the mortality rate was 13% (14 were intoxications with digoxin, 36 with digitoxin, 1 was mixed). Forty-five cases were suicide attempts; six were accidental overdosages. Since cardiac pacing may trigger fatal arrhythmia or delay the administration of Fab fragments, we conducted a retrospective study to determine whether fatal outcomes could be related either to cardiac pacing or to unsatisfactory use of immunotherapy. In our study, prevention of life-threatening arrhythmia failed in 8% of cases with Fab and in 23% with pacing. Though Fab tended to be more effective, this difference was not significant. In our study, the main obstacles to the success of Fab were pacing-induced arrhythmias and delayed or insufficient administration of Fab. Iatrogenic accidents of cardiac pacing were frequent (14/39, 36%) and often fatal (5/39, 13%). In contrast, immunotherapy was not associated with any serious adverse effects (0/28, 0%) and was safer than cardiac pacing (p < 0.05). In conclusion, during digitalis intoxication, the pacemaker has limited preventive and curative effects, is difficult to handle, and exposes patients to severe iatrogenic accidents. Fab fragments act as a powerful antidote and are safer and much easier to use than pacing. These results encourage us to prescribe Fab fragments as first-line therapy during acute digitalis intoxication.

Adult↗
PubMed2000

A non-fatal case of intoxication with foxglove, documented by means of liquid chromatography-electrospray-mass spectrometry.

The non-fatal self-poisoning of a 36-year-old female patient, who ingested a concoction of foxglove (Digitalis Purpurea), is presented. On the admission, initial symptoms were nausea and vomiting, abdominal pain, and cardiovascular shock with sinus bradycardia. Blood and urine were assayed for 17 cardiotonic hetorosides, using a highly specific LC-MS procedure. Serum and urine specimens were collected over five days and analyzed by liquid chromatography-electrospray-mass spectrometry (LC-ES-MS). This accurate procedure allowed the determination of the digitalis glycosides and their metabolites in serum and urine. The serum concentrations of digitalis glycosides were maximum on the first day (gitoxin 13.1 ng/mL, digitoxin 112.6 ng/mL, digitoxigenin 3.3 ng/mL, and digitoxigenin mono-digitoxoside 8.9 ng/mL) and decreased over five days. We observed a peak gitaloxin level (112.6 ng/mL) on the fifth day only. After administration of atropine as well as dimeticone, alginic acid, and metoclopramide, health status improved. The peak urine concentrations were reached at hour 30 and were respectively 91.3 and 69.9 ng/mL for gitaloxin and digitoxin, while those of digitoxigenin, digitoxigenin mono-digoxoside and gitoxin were lower (respectively 0.7, 1, and 5.6 ng/mL). The patient was discharged on the fifth day when there were no residual symptoms.

Adult↗
PubMed2000

Therapeutic drug monitoring on COBAS INTEGRA 400--evaluation results.

The COBAS INTEGRA 400 (Roche Diagnostics GmbH) is a random access analyzer with a consolidated test menue for routine clinical chemistry, specific proteins, drugs of abuse screening and therapeutic drug monitoring (TDM) and different measuring technologies. It was the aim of the present study to evaluate the suitability of this instrument as dedicated analyzer for TDM. Eight assays based on three different technologies were included: Acetaminophen (enzymatic method), Amikacin/ Phenytoin/ Free Phenytoin/ Lidocaine (fluorescence polarization immunoassays; FPIA), Digitoxin/Digoxin (kinetic interaction of microparticles in solution; KIMS). The study comprised the determination of imprecision according to NCCLS EP-T protocol, method comparison and linearity studies. The assays were compared with the corresponding methods on AxSYM or TDx analyzers (Abbott Laboratories). For Acetaminophen and Amikacin COBAS INTEGRA 700 was used as additional comparison instrument. The results are summarized in a table (table 6). Precision results are well acceptable with within-run CVs < 5% and total CVs < 6% except for Digitoxin and Digoxin which show a somewhat higher imprecision at low concentrations. Results obtained for Acetaminophen and Amikacin on COBAS INTEGRA 400 and 700 show excellent agreement. A good comparability is also found between COBAS INTEGRA 400 and AxSYM or TDx methods with slight systematic deviations for Acetaminophen, Amikacin and Free Phenytoin. The lower correlation coefficient for the digoxin method comparison can be attributed to two discrepant samples. Linearity throughout the range studied which covered > 80% of the measuring range was confirmed for the five assays tested (Digitoxin, Digoxin, Lidocaine, Free Phenytoin, Phenytoin) based on the acceptance criteria of +/- 10% deviation of the measured values from the theoretical values. Based on the analytical performance of the TDM tests studied it can be concluded that the COBAS INTEGRA 400 is very well suited for routine TDM analysis.

Drug Monitoring↗
PubMed1976

[New aspects on the mode of action of cardiac glycosides].

A dissociation of the therapeutic from the toxic effects of cardiac glycosides has repeatedly been described. Whereas it is generally accepted that the toxic effects of cardiac glycosides are based on an inhibition of the Na+-K+-ATPase, the mechanism of action of therapeutic concentrations of cardiac glycosides still remains uncertain. To test the hypothesis, that cardiac glycosides might be transported into a distinct compartment of the myocardium with the Na+-K-ATPase acting as a carrier, the interaction of some inhibitors of this enzyme (digitoxin, dihydroouabain, cassaine, N-ethylmaleimide, p-hydroxy-mercuribenzoate, ethacrynic acid, spironolactone) with ouabain was studied at different levels of cardiac glycoside actions: Myocardial function, cardiac uptake and subcellular distribution and binding to the Na+-K+-ATPase. The following results were obtained: All cardioactive drugs (ethacrynic acid and spironolactone showed no such effects) reduced dose-dependently the inotropic action of ouabain and in high concentrations increased its toxicity. The same drugs inhibited dose-dependently the cardiac uptake of ouabain without affecting the subcellular distribution pattern of ouabain. The binding of ouabain to the Na+-K+-ATPase was influenced in a similar way by these drugs, showing a competitive type of interaction with digitoxin, dihydroouabain and cassaine and a non-competitive mechanism with N-ethylmaleimide and p-hydroxymercuribenzoate. These results support the concept of a cardiac glycoside-ATPase interaction as a basis for the therapeutic action of these drugs. This may be explained either by a direct influence of cardiac glycosides on the ATPase activity and/or by a carrier mediated cardiac glycoside-transport into a distinct compartment of the myocardial cell.

Action Potentials↗
PubMed1985

Na/K/Cl cotransport in cultured human fibroblasts.

The transport characteristics and regulation of the Na/K/Cl cotransport system were investigated in cultured human fibroblasts (HSWP cells). The existence of the system was documented by the finding that digitoxin-insensitive K+ influx was dependent upon the presence of both Na+ and Cl- in the extracellular milieu. It was found that only Br- could partially substitute for Cl-, with SCN-, I-, acetate, and gluconate being ineffective. Li+ could partially substitute for Na+; however, choline was without effect. The shape of the titration curves for K+ influx versus extracellular Cl- concentration was dependent upon the substituted anion. Furthermore, the apparent Km for Cl- at saturating [K+]o and [Na+]o, was also dependent upon the substituted anion and ranged from 30 mM (gluconate substitution) to 100 mM (acetate substitution). The titration curves for K+ influx versus extracellular Na+ concentration displayed hyperbolic kinetics and the apparent Km = 15 mM at saturating [K+]o. The curve for K+ influx versus extracellular K+ concentration was a hyperbola and the apparent Km for K+ = 3 mM at saturating [Na+]o. The digitoxin-insensitive K+ flux was found to be sensitive to related 5-sulfamoylbenzoic acid derivatives, commonly known as "loop" diuretics and to be insensitive to both: amiloride (3,5-diamino-N-(aminoiminomethyl)-6-chloropyrazinecarboxamide++ +) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. The Na/K/Cl cotransport system was not stimulated by serum, but was slightly stimulated by two peptide mitogens. Furthermore, agents which cause an elevation in cellular cyclic AMP levels were found to be potent inhibitors of cotransport.

Biological Transport↗
PubMed1986

Characterization of two classes of cardiac glycosine binding sites in rat heart and brain membrane preparations, using quantitative computer modelling.

Cardiac glycoside binding to rat heart and brain membrane preparations was measured by a rapid filtration technique. Data were analysed using quantitative computer analysis. The experimental results were consistent with a model in which cardiac glycoside-specific binding occurs at two independent classes of sites. The high-affinity sites in heart membranes were characterized by dissociation constants (Kd) of 40, 50, and 61 nmol/l for ouabain, digoxin and digitoxin, respectively, and the lower-affinity sites were characterized by Kd of 2.3 mumol/l, 67 nmol/l and 71 nmol/l for ouabain, digoxin and digitoxin, respectively. Comparable results were obtained using brain membranes. Potassium ions inhibit [3H]-ouabain binding in a dose-dependent manner with an IC50 of 500 mumol/l. Quantitative computer modeling indicated that potassium inhibits ouabain binding to approximately the same extent at both classed of binding sites, consistent with the hypothesis that the two classes of binding sites for cardiac glycosides might be associated with the Na+K+-ATPase.

Animals↗
PubMed1985

[Medical treatment and long-term development of permanent reciprocal tachycardia in children. Apropos of 10 cases followed for 11 years].

Incessant reciprocating tachycardia (IRT) was diagnosed in 10 children aged 0-11 years (mean 2.5 years), followed-up for an average of 11 years (range 4-22 years). 8 children were treated for an average period of 2.8 years (range 0.5-6 years) with the association of amiodarone and digitoxine. All children were treated initially or secondarily with verapamil and/or betablockers with digitoxine for an average of 4.6 years (range 1-9 years). The true frequency of IRT, its tolerance and the age at diagnosis did not indicate the probable required length of treatment with amiodarone, but only the initial response to this drug. Finally, 5 patients were cured and in sinus rhythm, and the other 5 were well controlled, having only occasional bursts of tachycardia. When we compared one group of 5 cases with clinical signs of cardiac failure and radiological cardiomegaly (CTR greater than 0.60) with a second group of 5 cases in which the arrhythmia was better tolerated, surprisingly, the frequency of intreated IRT was not t he factor which influenced its tolerance (198/min vs 194/min). On the other hand, the following differences were observed between the two groups: a younger age at diagnosis in the first group (5 months vs 4.6 years) responsible for the longer follow-up period (14.5 vs 7 years), earlier treatment period with amiodarone (3.6 years compared to 5.5 years) and a longer treatment period with this drug (3.5 vs 2 years). It was only at about the age of 7 that this treatment could be withdrawn or changed with half the children completely cured, and the other half only controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1984

Drug interactions with nitrendipine.

Interactions between calcium channel blockers like nifedipine and concurrently administered drugs like digoxin or cimetidine have been described in the literature. Therefore, possible interactions of the new calcium channel blocker nitrendipine (20 mg daily) with digoxin (0.5 mg daily), digitoxin (0.1 mg daily), cimetidine (1,000 mg daily), ranitidine (300 mg daily), atenolol (100 mg daily), metoprolol (200 mg daily), and acebutolol (400 mg daily) were studied following 1 week of combined treatment of nitrendipine with each of these drugs. Six healthy volunteers were investigated (mean age, 30.2 +/- 2.1 years; mean body weight, 69.7 +/- 4.7 kg; means +/- SEM). Under nitrendipine monotherapy, maximum plasma levels (Cmax) averaged 41.6 +/- 12.8 ng/ml, and they were reached after 2 h. Mean area under the curve was 131.5 +/- 40 ng ml-1 h, and "oral" plasma clearance (Clpl) amounted to 80.8 +/- 27.5 L/h. The H2 receptor antagonists cimetidine and ranitidine and the digitalis glycosides like digoxin or digitoxin did not alter nitrendipine kinetics significantly. Also simultaneous treatment with beta-blockers did not significantly influence kinetic values of the calcium channel blocker, but atenolol showed a tendency to increase Cmax of nitrendipine to 54.2 +/- 19.7 ng/ml, when its Clpl was distinctly lowered to 42.7 +/- 10.4 L/h (p greater than 0.05 compared with 80.8 +/- 27.5 L/h under nitrendipine monotherapy). Increased digoxin plasma levels and digoxin-induced side-effects were seen under nitrendipine co-administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1982

Changes in myosin isozyme distribution induced by low doses of isoproterenol.

The Ca2+-activated myosin ATPase activity in isoproterenol-induced hypertrophied left ventricle increased by 20-30% while in Goldblatt rats hypertrophy occurred with a decreased myosin ATPase activity. In non-dissociating (pyrophosphate) gel electrophoresis isoproterenol treatment showed decreased V2 and V3 myosin isozymes; at the higher dose of isoproterenol (0.5 mg/kg body weight) only V1 was present. In contrast a shift toward the V3 isozyme is present in the ventricles of Goldblatt rats. One group of rats was treated with toxic doses of digitoxin: no hypertrophy occurred but there was a disappearance of V1 and V2 isozymes and a 50% decrease in Ca2+-activated ATPase activity. Thus low doses of isoproterenol produce hypertrophy with an isozyme pattern similar to that found in young (approximately 4-6 weeks old) rats. The results with digitoxin show that shifts in the cardiac isozyme distribution can occur without hypertrophy.

Adenosine Triphosphatases↗
PubMed1978

Pharmacological reevaluation of gitoxin in man.

The aim of the present investigation was to reevaluate the pharmacokinetic and pharmacodynamic parameters of gitoxin in man. Gitoxin given as a solution is quasi-completely absorbed after oral administration in a fasting man. A dose of 1.5 mg modifies the left ventricular ejection time index (LVETI) as digoxin or digitoxin does. The biological half-life of gitoxin calculated on the basis of plasma concentrations or urinary data is about one day. The urinary elimination of gitoxin is smaller than 21% of the dose. Therefore the two main advantages of gitoxin versus digoxin or digitoxin are: 1) its short biological half-life and 2) its elimination being less dependent on the renal function of the patient.

Administration, Oral↗
PubMed1980

Effect of inline filtration on the potency of low-dose drugs.

Simulating actual conditions of intravenous infusion, a number of routinely used additive drugs were tested for potential binding to an inline i.v. filter containing a cellulose ester membrane. Two infusion solutions, 5% dextrose and 0.9% sodium chloride, were used to deliver the drugs. Drug samples were assayed before and after passage through the filter by the following methods: bleomycin sulfate, cyanocobalamin, ergonovine maleate, mithramycin, vinblastine sulfate, and vincristine sulfate by direct spectrophotometry; oxytocin by biological assay; levarterenol by fluorescence; and folic acid, heparin, insulin, and digitoxin by radiotracer methods. Measurable reduction in potency occurred in both infusion solutions with digitoxin, insulin, mithramycin, and vincristine sulfate. No reduction in potency was observed in either infusion solution with bleomycin sulfate, cyanocobalamin, ergonovine maleate, folic acid, heparin, leverterenol bitartrate, oxytocin, and vinblastine sulfate. The study results indicate that the potency of drugs administered intravenously in small doses could be significantly reduced during inline filtration through a filter containing a cellulose ester membrane.

Filtration↗
PubMed1993

[Separation and identifying features of the cardiac aglycones and glycosides of Nerium oleander L. flowers by thin-layer chromatography].

The present work was aimed at extracting some cardiotonic glycosides from Nerium oleander L. (N.o.L.) flowers, free from phytosterols and their esters and at resolving themselves by thick- and thin-layer chromatography. This work may contribute to the scientific recognition of N.o.L. drugs in the field of forensic medicine. MATERIALS AND METHODS. Apparatus. Kieselgel F254 thin-layer (250 mu) and Kieselgel thick-layer (2 mm) glass plates were used. MATERIALS. Chromatographic solvents were used; detectors were p-toluene sulphonic acid (PTSA) and antimony trichloride (SbCl3). STANDARDS. The following standards were used: gitoxigenin, oleandrin, digitoxin, and stigmasterol. Standard solutions were prepared at a M-3 concentration. The solvent system is described in Table I. EXTRACT. The extract was prepared using a mixture of solvents (hexane-diethylether-acetic acis, 50:50:1 v/v). With this mixture we noted that, in thin-layer chromatography, the used standards remained at the origin, while phytosterols and their esters migrated. White flowers of N.o.L. were air dried in the shade at room temperature, powered, and macerated in hexane-diethylether acetic acid for 24 hours. After removal of the phytosterols the remacerating powder was further percolated using a chloroform-methanol mixture (1:1.7 v/v) in order to extract the aglycone and the cardiac glycosides. As the medium's thin-layer chromatogram showed the absence of corresponding spots to test samples, the chloroform-methanol media were combined and evaporated under vacuum. The residue was redissolved in the chloroform-methanol mixture. The obtained extract concentration consisted of 5 grammes of dried flowers in 1 milliliter of solution, called extract E (Fig. 1). RESULTS. The results are reported in Figures 2 and 4 and in Table II (see text for explanation of symbols). Extract E (Fig. 2) and the F1, F2, and F3 concentrated fractions were examined by thin-layer chromatography (Fig. 1 and 3). Only the F3 fraction revealed compounds with the same chromatographic path and colours (detected by PTSA and SbCL3) as the reference standards gitoxigenin, oleandrin, and digitoxin. This finding was confirmed by using five different solvent-systems (Fig. 4). DISCUSSION AND CONCLUSION. The present study shows that the cardiac steroids and other constituents of Nerium oleander's flowers are separated in three fractions by thick-layer chromatography free from phytosterols and their esters. This result may have useful implications in the fields of analytical toxicology and forensic medicine and potential application in clinical practice given that cytotoxic and antileukemic activities of the extracts from plants containing cardiac glucosides have been reported.

Cardiac Glycosides↗
PubMed1977

[Pharmacokinetics of cardiac glycosides and clinical consequences].

The purpose of pharmacokinetics of cardiac glycosides is to study the time courses of glycosides in biological fluids, tissues and excreta. The extent of accumulation of a given dose at uniform time intervals depends only from the overall elimination rate constant. By knowing the elimination rate constant the extent to which a cardiac glycoside would accumulate in the body following a fixed dosing regimen can be calculated. The higher accumulation in the central nervous system requires a much longer time. Therefore it may be assumed that the brain is a deep compartment for cardiac glycosides and this compartment cannot be detected by analysis of plasma glycoside concentrations. Central side effects of cardiac glycosides may occur at therapeutic plasma levels. In renal disease a lower maintenance dose of digoxin and methyldigoxin should be administered or the same dose less frequently. Digitoxin does not accumulate in patients with renal failure or in anuria since the extrarenal elimination of digitoxin is much higher compared to digoxin and methyldigoxin.

Biological Availability↗
PubMed1996

Effect of antibody specificity on results of selected digoxin immunoassays among various clinical groups.

We examined the specificity of three automated digoxin immunoassays (Abbott TDxFLx Digoxin II assay, Baxter-Dade Stratus II Digoxin assay, and Ciba Corning ACS Digoxin assay) applied without modification to (a) sera from 229 digoxin-free patients in 12 cohorts associated with nonspecific or endogenous digoxin-like immunoreactive factor (DLIF) interference, and (b) drug-free serum supplemented with the major metabolites and analogs of digoxin. We observed three patterns of apparent digoxin results among the DLIF samples: one common to kidney and liver failure patients, where TDx and Stratus assays showed significant positive results; one common to newborns and cord blood, where only the TDx assay had significant interference; and one from cardiac surgery patients, where the Stratus assay alone showed interference. Of the three assays, the ACS had the least interference from DLIF. The assays also behaved differently with respect to cross-reactivity with digoxin metabolites, digitoxin, and digitoxin metabolites. The ACS assay again had the least analog or metabolite cross-reactivity. The three methods agreed well on digoxin-positive specimens, with a mean bias of <0.15 microgram/L digoxin for each and discrepancies (defined as >3 SD between the assay pairs compared) of only 3-5%.

Antibody Specificity↗