digoxin and Liver-Diseases

It is confirmed by several studies that in normal subjects a substance recognized by antibodies anti digoxin exists. Such a substance can be found at increased concentration in pregnant women, neonates, in liver or kidney diseases. A limited increase in concentration has been also registered in patients with essential hypertension and in normotensive patients with a family history of hypertension. Serum or urines rich in such a substance show an increased capacity of inhibiting in vitro the sodium-potassium pump and therefore in reducing also in vivo the capacity of reabsorption of sodium and with it, of water. The investigators interest for this substance has two main reasons: 1) the interference that such a substance has in dosages of digitalis in therapeutic monitorizing; 2) the possibility that such a substance has an important physiological role in hydroelectrolytic metabolism.

Topics: Adult; Cardenolides; Digoxin; Enzyme Inhibitors; Female; Humans; Hypertension; Infant, Newborn; Kidney Diseases; Liver Diseases; Male; Saponins; Sex Factors

Topics: Digoxin; Humans; Liver Diseases

Topics: Adult; Digitalis Glycosides; Digoxin; Female; Humans; Hypertension; Infant, Newborn; Kidney Failure, Chronic; Liver Diseases; Male; Pregnancy

Urapidil is a selective alpha 1-adrenoceptor antagonist with central antihypertensive action which is increasingly used in the treatment of hypertension. Urapidil is readily absorbed, is subject to moderate first-pass metabolism and is eliminated primarily as metabolites of much lower antihypertensive activity than the parent drug. The influences of age, renal and hepatic disease on the disposition of urapidil are reviewed. Studies on the relationship between pharmacodynamics and pharmacokinetics show that the optimum use of urapidil in clinical practice depends on an understanding of the pharmacokinetic properties of the drug.

Topics: Adult; Aged; Aged, 80 and over; Aging; Digoxin; Drug Interactions; Half-Life; Humans; Hypertension; Kidney Diseases; Liver Diseases; Male; Middle Aged; Piperazines

Various laboratories have reported endogenous digoxin-like immunoreactive factor(s) (DLIF) in blood from patients in renal failure or liver failure, from newborn infants, and from third-trimester pregnant women. Similar immunoreactivity has been detected in amniotic fluid, in cord blood, and in urine and serum from normal subjects. The factor(s) giving rise to this immunoreactivity cross react with antibodies used in many currently available immunoassays for digoxin, sometimes causing apparent digoxin concentrations exceeding the therapeutic range obtained for exogenous digoxin, with consequent errors in measurement and in subsequent clinical interpretation of digoxin results. Here, I summarize findings in our laboratory and those of others. DLIF evidently exist in three states in serum: tightly protein-bound, weakly protein-bound, and unbound (free). In normal subjects, greater than 90% of the total DLIF in serum is tightly but reversibly bound to serum proteins and is not readily detectable by direct measurement of digoxin in serum with conventional immunoassays. However, there seems to be a redistribution of the more weakly bound and unbound components in patients with renal failure, pregnant women, and newborns. The increased values detected in these groups are ascribable to increased amounts of weakly bound and unbound DLIF rather than to increased total DLIF. Carrier proteins may play a prominent role in the transport of these factors in blood. I discuss the potential physiological and pharmacological implications of detecting endogenous immunoreactive factors that cross react with antibodies to drugs.

Topics: Adult; Animals; Blood Proteins; Cardiovascular Physiological Phenomena; Chemical Phenomena; Chemistry, Physical; Digoxin; Extracellular Space; False Positive Reactions; Female; Fetal Blood; Humans; Immunoassay; Infant, Newborn; Kidney Diseases; Liver Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Protein Binding; Water-Electrolyte Balance

The calcium entry blockers are used in a wide variety of clinical situations. Coexisting disease states, such as renal or hepatic dysfunction, may require individualized dosing of these agents. The physiologic changes associated with aging may also affect the pharmacokinetic properties of the drugs. If calcium entry blockers are used concurrently with other medications, dosage adjustment or selection of an alternative drug may be needed. Drug interactions between calcium entry blockers and cimetidine, digoxin and quinidine appear to be clinically significant. Individualized dosing in patients who have coexisting disease or who are using other medications is essential to achieve an adequate therapeutic response and avoid adverse effects. Considerations to attain an optimal response in such situations are presented.

Topics: Adult; Age Factors; Aged; Calcium Channel Blockers; Child; Cimetidine; Diabetes Complications; Digoxin; Drug Interactions; Female; Humans; Hypertension; Kidney Diseases; Kinetics; Lactation; Liver Diseases; Middle Aged; Pregnancy; Quinidine; Smoking

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Bile; Biological Transport; Cardiac Glycosides; Contraceptives, Oral, Hormonal; Diazepam; Digoxin; Enterohepatic Circulation; Fluorenes; Half-Life; Hexamethonium Compounds; Humans; Imipramine; Indocyanine Green; Kidney Diseases; Liver Diseases; Molecular Weight; Pharmaceutical Preparations; Spironolactone

Topics: Biotransformation; Cytochrome P-450 Enzyme System; Diazepam; Digitoxin; Digoxin; Drug Interactions; Drug Therapy; Drug Therapy, Combination; Enzyme Induction; Ethanol; Kidney; Kidney Diseases; Liver; Liver Diseases; Nordazepam; Receptors, Drug

Topics: Animals; Body Weight; Digitalis Glycosides; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic; Liver Diseases; Myocardial Contraction; Protein Binding; Structure-Activity Relationship; Thyroid Diseases; Tissue Distribution

Topics: Administration, Oral; Aged; Digitalis Glycosides; Digitoxin; Digoxin; Feces; Heart Atria; Heart Failure; Humans; Injections, Intramuscular; Injections, Intravenous; Intestinal Absorption; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Obesity; Tachycardia; Thyroid Diseases; Tritium; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Administration, Oral; Arrhythmias, Cardiac; Digitoxin; Digoxin; Drug Interactions; Electric Countershock; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Liver Diseases; Malabsorption Syndromes; Pharmaceutical Vehicles; Phenytoin; Potassium; Thyroid Diseases

Topics: Age Factors; Arrhythmias, Cardiac; Calcium; Child; Coronary Care Units; Digitalis Glycosides; Digoxin; Electric Countershock; Electrocardiography; Endocrine System Diseases; Heart Diseases; Heart Failure; Heart Rate; Heart Valve Diseases; Humans; Kidney Failure, Chronic; Liver Diseases; Lung Diseases; Magnesium; Obesity; Ouabain; Poisoning; Potassium; Psychophysiologic Disorders; Pulmonary Heart Disease; Thyroid Diseases; Time Factors

The bioavailability of digoxin and beta-methyl-digoxin (BMD) was tested with a single dose on the grounds of peak serum concentration, tmax, area under the serum concentration-time curve and the cumulative 24 hour urinary excretion on one group of patients with liver disease (n = 20) and one with gastrointestinal disease (n = 10). Despite the smaller dose (0.5 mg BMD against 0.75 mg digoxin), peak serum concentration was significantly higher with BMD in both groups and was also reached earlier than with digoxin. The extent of absorption was also higher in both groups with BMD than with digoxin. A comparison of the results on hand with the results obtained in corresponding tests on healthy persons showed no significant differences with BMD. The excellent bioavailability of BMD was therefore also proved on patients with gastrointestinal diseases, whereas with digoxin the absorption in these patients was retarded, compared with healthy persons, but the extent of absorption was not reduced either. In gastrointestinal diseases with unknown conditions of absorption, the better bioavailability of BMD is probably of advantage, when compared with digoxin. According to medical literature, t/2 of BMD may be prolonged in liver diseases, so that in such cases the dose of BMD has to be adjusted or the use of digoxin is recommended.

Topics: Adult; Aged; Biological Availability; Digoxin; Female; Gastrointestinal Diseases; Humans; Liver Diseases; Male; Medigoxin; Middle Aged

Although the possible interference of digoxin-like immunoreactive substances (DLIS) on the Architect iDigoxin chemiluminiscent microparticle immunoassay (CMIA) has been emphasized by the manufacturer, a specific study about this subject has still not been carried out.. Apparent serum digoxin concentrations were determined using the Architect iDigoxin CMIA from Abbott Laboratories in digoxin-free pregnant women (n = 50), and patients with liver disease (n = 50), renal insufficiency (n = 50), kidney (n = 25) or liver (n = 25) transplant, and critical illness (n = 50).. In all of the patients included in this study, apparent serum digoxin concentrations were lower than the correspondent quantification limit (< 0.30 microg/L).. The Architect iDigoxin CMIA assay would be relatively free from endogenous DLIS positive interferences.

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Digoxin; Female; Humans; Kidney Transplantation; Liver Diseases; Liver Transplantation; Male; Middle Aged; Pregnancy; Renal Insufficiency

We compared digoxin-like (DLIS) and digitoxin-like (DTLIS) immunoreactive substance concentrations for 30 people older than 65 years with those for 25 people younger than 50. None received digoxin or had liver disease, uremia, or volume expansion. We found no DTLIS in any specimen, and only 1 specimen from an elderly person demonstrated a low DLIS concentration. In addition, for 22 non-volume expanded patients (8 younger than 50 years and 14 older than 65) receiving digoxin, the fluorescence polarization (FPIA) and the microparticle enzyme (MEIA) immunoassays revealed comparable serum digoxin concentrations, indicating an insufficient DLIS concentration to interfere with digoxin immunoassay results. Therefore, elderly people who are not volume expanded do not have elevated DLIS or DTLIS concentrations. Furthermore, for patients with liver disease or uremia (18 older than 65 years and 20 younger than 50), the DLIS and DTLIS concentrations were elevated. Finally, for 5 patients with liver disease who received digoxin, serum digoxin concentrations were lower by MEIA and higher by FPIA, indicating the patients had elevated DLIS levels that interfered with the assays. Elevated DLIS and DTLIS concentrations are associated with volume expansion and not age.

Topics: Aged; Aging; Blood Volume; Digitoxin; Digoxin; Female; Fluorescence Polarization; Humans; Immunoenzyme Techniques; Liver Diseases; Male; Middle Aged; Uremia

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.

Topics: Cross Reactions; Digoxin; False Positive Reactions; Fluorescence Polarization Immunoassay; Humans; Immunoenzyme Techniques; Liver Diseases; Microspheres; Uremia

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.

Topics: Adult; Antibodies, Monoclonal; Calibration; Digoxin; Female; Humans; Immunoassay; Kidney Diseases; Liver Diseases; Pregnancy

Endogenous digoxin-like immunoreactive factors (DLIF) can interfere with some digoxin immunoassays. We looked for similar interference, called digitoxin-like immunoreactive factors (DTLIF) in two digitoxin immunoassays: A new chemiluminescent assay (CLIA), processed on the automated random access immunoassay system ACS:180, and a fluorescent polarization assay (FPIA), processed on the semiautomated TDx batch analyzer. One hundred thirty-seven samples of sera were tested from nondigitalized pregnant women, patients with liver or kidney diseases, and cord blood. The CLIA digitoxin assay uses a murine monoclonal antibody and requires no sample pretreatment; the FPIA digitoxin assay uses a polyclonal rabbit antibody and requires sample precipitation. Both assays have a similar dynamic range and sensitivity and give comparable results with commercial controls and external quality control survey samples. Although the CLIA detected no digitoxin in any sample tested, the FPIA showed apparent digitoxin concentrations of more than 2.0 ng/ml for 100% and 44% among cord blood and liver disease specimens, respectively. The highest DTLIF concentration was found in serum from a patient with liver disease (18.1 ng/ml). When spiked with 32 ng/ml digitoxin, six of the samples containing DTLIF generated FPIA digitoxin values of 6% to 27.5% more than the expected digitoxin levels. Two specimens with no detectable DTLIF activity were run as controls, and when spiked with digitoxin, showed target digitoxin concentrations in the FPIA. The CLIA recovered near the target digitoxin values (32 ng/ml) in all spiked samples. It was concluded that the polyclonal FPIA digitoxin assay may give discordant digitoxin concentrations in some patient groups because of interference from digitoxin-like immunoreactive factors. The CLIA digitoxin assay is not affected by DTLIF interference.

Topics: Antibodies, Monoclonal; Cardenolides; Digitoxin; Digoxin; Female; Fetal Blood; Fluorescence Polarization; Fluorescence Polarization Immunoassay; Humans; Immunoassay; Kidney Diseases; Liver Diseases; Luminescent Measurements; Pregnancy; Saponins; Sensitivity and Specificity; Uremia

Digoxinlike immunoreactive substances (DLIS) cross-react with antidigoxin antibodies and falsely elevante total digoxin levels. Cross-reactivity of DLIS with various immunoassays for digoxin has been extensively studied in the past. The digitoxin molecule differs from digoxin by having one extra hydroxyl group in the aglycone ring. Therefore, DLIS may also falsely elevate total digitoxin concentrations. However, in the past, limited studies have shown the presence of digitoxinlike immunoreactive substances (DTLIS) in cord blood and sera of neonates. We compared DLIS and DTLIS concentrations in sera of patients with uremia, liver disease, and hypoalbuminemia. We found measurable DLIS concentrations in 11 of 45 patients by the fluorescence polarization immunoassay (FPIA) for digoxin (range, 0.20-0.89 ng/ml digoxin equivalent). These patients did not receive any digoxin or digitoxin. Using the FPIA, we also found elevated DTLIS concentrations in 10 of these 45 patients (range, 2.88-21.24 ng/ml digitoxin equivalent). Given the narrow therapeutic range of digitoxin (15-30 ng/ml), this cross-reactivity is significant. Elevated concentrations of DTLIS in sera falsely elevated the measured concentrations of digitoxin (positive interference) when known amounts of digitoxin were added to such sera. Interestingly, we found a poor correlation between DLIS and DTLIS concentrations in sera of patients with liver disease and uremia (r = 0.58), with some patients having no measurable DLIS activity but measurable DTLIS activity and vice versa. Digoxin showed only 4-8% cross-reactivity against digitoxin antibody with a wide range of concentration. Some proposed DLIS compounds (nonesterified fatty acids, cholic acid, lysophospholipid, and DHEA-sulfate) did not show any cross-reactivity with the digitoxin assay at a concentrations much higher than the physiologic range. We conclude that DTLIS activity is present in patients with liver disease and uremia, and the correlation between DLIS activity and DTLIS activity is poor. Moreover, some proposed DLIS do not explain the DTLIS activity detected in serum.

Topics: Digitoxin; Digoxin; Fluorescence Polarization Immunoassay; Humans; Liver Diseases; Uremia

A comparison of the results of a newly developed fluorescence-derivatization/HPLC method and a commercial immunoassay method (ACA, Dupont) for the measurement of serum digoxin concentrations in patients indicates that (1) the results from the ACA method agree well with those from the HPLC method in patients with cardiovascular disease but without renal, diabetic, and liver disease, (2) serum digoxin concentrations determined by the ACA method are overestimated in patients with renal, diabetic, or liver disease, and (3) the steady-state serum concentrations of hydrolyzed and reduced metabolites are relatively insignificant in patients receiving digoxin therapy, including patients with renal failure. The excellent reproducibility of the HPLC and immunoassay methods (coefficient of variation < 9.0%), together with the demonstrated specificity of the HPLC method with respect to potential interference from digoxin metabolites, endogenous digoxin-like immunoactive substances, and coadministered drugs and their metabolites, allows quantitation of the degree of interference in digoxin immunoassays under actual therapeutic drug monitoring conditions. Clinically significant interferences (0.3 to 1.1 ng/ml) with immunoassay determination were found in the majority of patients in all three diseases studied.

Topics: Adult; Aged; Cardiotonic Agents; Chromatography, High Pressure Liquid; Diabetes Mellitus; Digoxin; Female; Fluorescence; Humans; Immunoassay; Kidney Diseases; Liver Diseases; Male; Middle Aged

Performance characteristics of the Abbott nonpretreatment AxSYM Digoxin II assay were evaluated for quantification of digoxin at four independent sites. Correlation of digoxin measurements with the Abbott pretreatment AxSYM, Baxter Stratus II, Abbott TDx/ TDxFLx II, Abbott IMx, Emit 2000, and Beckman Synchron CX digoxin assays showed acceptable agreement, as indicated by: slope values > 0.84, r > 0.90, y-intercepts for all comparisons at or below the assay detection limit, and Sy/x ranging between 7.5% and 15.4% of the average digoxin value. Susceptibility to interference from digoxin-like immunoreactive factors (DLIFs) was examined in 233 samples from renal patients, liver disease patients, cord blood, and third-trimester pregnancies; the AxSYM Digoxin II assay demonstrated the least DLIFs interference. DLIF susceptibility for four of the methods was significantly greater (P < 0.05) than in the AxSYM Digoxin II assay; susceptibilities of the Stratus II and Emit 2000 methods were similar to the AxSYM Digoxin II assay.

Topics: Autoanalysis; Automation; Digoxin; False Positive Reactions; Female; Fetal Blood; Humans; Immunoassay; Immunoenzyme Techniques; Indicators and Reagents; Kidney Diseases; Liver Diseases; Pregnancy; Pregnancy Trimester, First; Regression Analysis; Reproducibility of Results

Comparison of a new monoclonal digoxin assay with three polyclonal digoxin assays for their cross-reactivity to digoxin-like immunoreactive factors (DLIF) and digoxin metabolites.. Sixty-six nondigitalized patient samples from 5 different groups: neonates, women in 3rd trimester pregnancy, and patients with liver or renal diseases, or undergoing organ transplants, and 139 samples from digoxin-treated patients of 4 categories (hospital sick, liver, renal, and outpatients) were compared in 4 different digoxin assays: (a) ACS Digoxin (ACS) developed for the automated chemiluminescent Ciba Corning ACS 180 system, (b) Baxter Stratus (Stratus, a fluoroimmunoassay), (c) Ciba-Corning Magic (Magic, a radioimmunoassay), and (d) an in-house radioimmunoassay (RIA). The ACS and RIA were also compared for their cross-reactivity to four principal digoxin metabolites.. Among the nondigitalized specimens, no significant DLIF interference was found for all 4 assays among the pregnant women or liver and transplant patients. However, the neonates registered high DLIF interference with Magic and RIA, but none for ACS or Stratus. DLIF interference in renal samples was highest in the Magic assay and lowest in RIA. Among the specimens with digoxin, a higher number of discrepant samples were found from the sick patients than from outpatients. In 75% of such discrepant samples, the ACS result was less than other assay results, suggesting DLIF as the probable cause. The two assays differed most in their cross-reactivity to the deglycated metabolites, digoxigenin and its mono-digitoxoside.

Topics: Adult; Antibodies, Monoclonal; Cross Reactions; Digoxin; Female; Fluoroimmunoassay; Humans; Immunoassay; Infant, Newborn; Kidney Diseases; Liver Diseases; Luminescent Measurements; Male; Organ Transplantation; Pregnancy; Radioimmunoassay; Sensitivity and Specificity

Five immunoassays for the determination of digoxin have been evaluated (Digoxin II, Abbott; Cedia Digoxin XL, Microgenics; Coat-a-Count Digoxin, Diagnostic Procedure Corporation, DPC; "On-line" Digoxin, Roche Diagnostic Systems; EMIT 2000 Digoxin, Syva). Four of them required no sample pre-treatment. The methods included a radioimmunoassay, fluoroimmunoassay, two enzyme-immunoassays and a turbidimetric immunoassay: the last three mentioned were adapted to the Cobas Mira Plus. The intra- and inter-assay precision was lower than 9%, except for Microgenics. The calibration stability fluctuated from 120 days for Abbott to 27 days for the Roche test, 7 days for the Syva assay and 2 days for Microgenics. The DPC test was not assayed for calibration stability. The interference from "digoxin-like immunoreactive factor(s)" differed according to the assay. The highest interference was seen with Abbott and Microgenics, and the lowest with the DPC test. The comparison among all the methods offered values of "r" higher than 0.95 except Microgenics and Syva assays where "r" was 0.896. The results obtained with Roche and Microgenics were higher than 12% of the remaining assays.

Topics: Digoxin; Female; Fetal Blood; Humans; Immunoassay; Infant, Newborn; Kidney Diseases; Liver Diseases; Pregnancy; Reagent Kits, Diagnostic

Topics: Antibody Specificity; Blood Proteins; Cardenolides; Digitoxin; Digoxin; Female; Fetal Blood; Humans; Immune Sera; Kidney Diseases; Liver Diseases; Pregnancy; Saponins

Increased levels of a circulating digoxin-like factor (DLF) occur in a number of physiologic states in which sodium homeostasis is altered, and may contribute to the pathogenesis of hypertension. We exploited the different affinities for DLF of seven antisera directed at digoxin to develop an immunochemical profile, and then employed this index to address two questions: does the same DLF species exist in several conditions associated with increased DLF levels, including pregnancy, renal failure, hepatic failure, and neonatal cord blood? Will this approach prove useful in assessing candidates proposed to be DLF? An identical profile was identified in serum from pregnant women and patients with renal or hepatic failure, and a highly significant correlation existed between DLF levels measured with antisera of high and intermediate affinity in 42 subjects with increased levels (r = 0.93; P less than .001). In patients with renal failure, when endogenous DLF levels were too low to assess the profile, concentration of the serum resulted in measurable DLF levels that had an identical profile. The profile was somewhat altered in umbilical cord blood, perhaps reflecting an influence of increased steroid hormone levels. Among agents suggested as candidates for DLF, neither lysophosphatidylcholine nor ouabain showed a profile resembling DLF. Progesterone, 17-OH-progesterone, and bufalin, on the other hand, did show substantial similarity, perhaps providing a clue to the structure of DLF. The normal plasma levels of progesterone and 17-OH-progesterone are 100- to 1000-fold too low to be candidates for DLF and bufalin was sufficiently dissimilar not to be a candidate. DLF in at least three different patient populations probably represents identical chemical species.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies; Antibody Affinity; Antibody Specificity; Blood Proteins; Bufanolides; Cardenolides; Digoxin; Female; Fetal Blood; Humans; Kidney Diseases; Liver Diseases; Pregnancy; Progesterone; Radioimmunoassay; Saponins

Digoxin-like immunoreactive substances are an endogenous group of compounds that cross-react in conventional immunoassays for digoxin. Plasma digoxin-like immunoreactive substance concentrations were estimated using the Abbott TDxll fluorescence polarisation immunoassay kit for digoxin. Digoxin-like immunoreactive substances were measured in one hundred consecutive Intensive Care Unit (ICU) patients who were not treated with digoxin. One hundred healthy blood donors were used as controls. Thirty of the ICU patients had plasma digoxin-like immunoreactive substance concentrations greater than or equal to the greatest value found in the control group (0.22 nmol/l). In the ICU group the median value was 0.17 nmol/l and the range zero to 1.69 nmol/l. In the control group the median was less than the limit of detection of the assay, and the range zero to 0.22 nmol/l. Sixteen ICU patients had coexisting renal and hepatic dysfunction and this group had a median digoxin-like immunoreactive substance concentration of 0.21 nmol/l (range zero to 1.69 nmol/l), while 38 patients with hepatic dysfunction and normal renal function had a median concentration of 0.17 nmol/l (range zero to 0.77 nmol/l). In contrast four patients with renal dysfunction only had a median concentration of 0.05 nmol/l (range zero to 0.34 nmol/l). The remaining forty-two patients had neither hepatic nor renal dysfunction and this group had a median concentration of 0.15 nmol/l (range zero to 0.36 nmol/l). This study has identified the critically ill as a group of patients who exhibit measurable plasma digoxin-like immunoreactive substances using the most commonly used kit for analysis of digoxin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Proteins; Cardenolides; Critical Care; Digoxin; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Reagent Kits, Diagnostic; Saponins; Sodium-Potassium-Exchanging ATPase

This report demonstrates the questionable usefulness of monitoring digoxin concentrations using the available immunoassays in some clinical situations. The patient reported here showed three characteristics (being a neonate with hepatic and renal impairment) that are associated with the presence of digoxin-like immunoreactive substances. The patient's serum digoxin concentration continued to rise to a peak of 43.7 nmol/L (34.1 ng/mL), 19 days after administration of the drug was discontinued.

Topics: Digoxin; Humans; Infant, Newborn; Kidney Diseases; Liver Diseases; Male

1. This study compared the analysis of digoxin using a high-performance liquid chromatographic post-column derivatization (HPLC-PC) assay and the TDx fluorescence polarization immunoassay (FPIA). 2. Serum obtained from 15 digitalized patients showed higher mean digoxin levels with the FPIA method as compared to the HPLC-PC procedure such that the mean HPLC-PC/FPIA ratio was 0.91 +/- 0.14 (mean +/- SD). Demonstrated cross-reactivity of digoxin metabolites with the FPIA is probably responsible for this observation. 3. Cross-reactivity of the immunoassay towards endogenous material present in serum samples from certain patient groups was an even greater problem, with apparent 'digoxin' serum concentrations in untreated hepatic failure patients being within the therapeutic range for digoxin. 4. The HPLC-PC method did not suffer from such interference and would therefore provide more accurate values for patients where high levels of interference could contribute to false digoxin levels.

Topics: Chromatography, High Pressure Liquid; Digoxin; False Positive Reactions; Fetal Blood; Fluorescence Polarization; Humans; Immunoassay; Kidney Diseases; Liver Diseases

Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 +/- 0.05 ng per ml, p less than 0.01) was higher than that of controls (0.02 +/- 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 +/- 0.17 ng per ml, p less than 0.001), hepatorenal syndrome (0.57 +/- 0.20 ng per ml, p less than 0.001) and hepatic encephalopathy (0.43 +/- 0.20 ng per ml, p less than 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 +/- 0.06 ng per ml, p less than 0.001) before the development of clinically detectable ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chronic Disease; Creatinine; Digoxin; Humans; Liver Diseases; Radioimmunoassay; Sodium

Topics: Acute Disease; Adult; Aged; Canrenoic Acid; Chronic Disease; Digoxin; False Positive Reactions; Female; Humans; Immunoenzyme Techniques; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Pregnadienes; Radioimmunoassay; Random Allocation

Topics: Blood Proteins; Cardenolides; Digoxin; Humans; Liver Diseases; Saponins

The effect of renal and/or hepatic dysfunction, and of concomitant spironolactone therapy, on seven commercial digoxin assays was evaluated in 45 patients taking both these drugs, and a comparison made with the digoxin concentrations measured using the same assays in 30 patients taking digoxin in the absence of spironolactone. The study showed that increasing renal dysfunction resulted in increasing inaccuracy in assay results with the methods tested. The influence of concomitant spironolactone was to produce a further distortion, which was shown to be additive in patients with impaired renal and/or liver function. The results highlight the unresolved specificity problems which persist in many, if not all, of the immunoassays currently offered to clinical laboratories which, if not recognised, could significantly influence digoxin therapy and patient management.

Topics: Aged; Aged, 80 and over; Digoxin; Female; Humans; Immunoassay; Kidney Diseases; Liver Diseases; Male; Middle Aged; Spironolactone

The incidence and magnitude of false-positive serum digoxin concentrations (SDCs) determined by three digoxin assays in patients with liver disease were studied. Patients with biochemical evidence of liver disease were enrolled in the study if they had never received a cardiac glycoside, were not pregnant, were not receiving spironolactone, did not have moderate to severe renal impairment, and did not have transient elevations in liver function test results. Blood specimens from each patient were assayed for apparent SDCs in triplicate using a fluorescence polarization immunoassay (FPIA, TDx Digoxin II, Abbott) and a digoxin radioimmunoassay (RIA, GammaCoat I125, Clinical Assays) and in duplicate using a fluorometric enzyme immunoassay (Dade Stratus, American Dade). Forty-two patients met the study criteria. The percentage of patients exhibiting detectable apparent SDCs (greater than or equal to 0.2 ng/mL) was 57% with RIA, 55% with FPIA, and 28% with the fluorometric enzyme immunoassay. Apparent SDCs ranged from 0.2 to 0.6 ng/mL (RIA), 0.2 to 1.56 ng/mL (FPIA), and 0.2 to 0.38 ng/mL (fluorometric enzyme immunoassay). Values obtained using the fluorometric enzyme immunoassay were significantly different from the apparent SDCs determined using RIA and FPIA; however, no significant difference was found between the values obtained using RIA and FPIA. Significant correlations were found between the apparent SDCs determined using RIA and serum bilirubin values and between the apparent SDCs determined using the fluorometric enzyme immunoassay and alkaline phosphatase values. Of the three assay methods tested, the fluorometric enzyme immunoassay showed the least cross-sensitivity to digoxin-like immunoreactive substance (DLIS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Digoxin; False Positive Reactions; Female; Humans; Liver Diseases; Male; Middle Aged; Radioimmunoassay

Topics: Autoanalysis; Blood Proteins; Cardenolides; Digoxin; False Positive Reactions; Humans; Immunoenzyme Techniques; Liver Diseases; Saponins

A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration.

Topics: Acute Kidney Injury; Adult; Cerebral Hemorrhage; Chromatography, High Pressure Liquid; Cross Reactions; Diabetes Mellitus, Type 1; Digoxin; False Positive Reactions; Fluorescent Antibody Technique; Humans; Hypertension; Immunoassay; Liver Diseases; Male; Radioimmunoassay; Renal Dialysis

Falsely elevated serum digoxin values have recently been reported in patients with liver disease. Since not all patients have circulatory digoxin-like immunoreactive substance (DLIS) in their serum, we compared the clinical and laboratory findings in patients with and without DLIS. Thirty-two patients with liver disease were studied. The only parameter that was significantly different in the two groups was serum bilirubin. In the group of patients with DLIS, significant correlations were obtained between DLIS and bilirubin and DLIS and creatinine. We postulate that increased levels of DLIS in serum are due to an abnormality of DLIS excretion.

Topics: Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Blood Proteins; Cardenolides; Creatinine; Digoxin; Female; Humans; L-Lactate Dehydrogenase; Liver Diseases; Male; Middle Aged; Prothrombin Time; Radioimmunoassay; Saponins; Serum Albumin

In ten patients suffering from moderate to severe disturbances of liver function (hepatic cirrhosis, carcinomatous metastases of the liver) the elimination of 16-acetyl-gitoxin from plasma was measured after a single oral dose of 1.2 mg pengitoxin. In 9 of 10 patients the mean half-life amounted to 67.3 h (SD 14.2 h). In one patient with carcinomatous infiltration of the liver and concomitant cirrhosis, the half-life was prolonged to 165.3 h. The results point to an unchanged elimination of 16-acetyl-gitoxin in patients suffering from liver cirrhosis.

Topics: Acetyldigoxins; Adult; Aged; Biotransformation; Digoxin; Half-Life; Humans; Liver Diseases; Middle Aged

The effect of encainide administration on steady-state plasma digoxin levels was evaluated in 17 patients receiving stable doses of digoxin. A paired t test, comparing plasma digoxin levels (mean +/- standard error) before encainide therapy (1.05 +/- 0.14 ng/ml) and after 2 weeks of encainide, 100 mg/day (1.03 +/- 0.11 ng/ml) or 200 mg/day (1.2 +/- 0.2 ng/ml), indicates no significant (p greater than 0.05) change in digoxin levels. These results were confirmed in a second study of 10 patients with severe congestive heart failure. Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required. Plasma concentrations of encainide and its 2 major metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide, significantly increased by 31.6%, 43.1% and 35.6% after concomitant cimetidine administration in 13 healthy adult men receiving 75 mg/day of encainide. However, a retrospective evaluation of 33 patients receiving both drugs did not reveal any clinically significant interactions. Retrospective evaluation of patients enrolled in clinical studies who received concomitant digoxin (268), antiarrhythmics (118), anticoagulants (78), antidiabetics (40), antipsychotics (23), beta blockers (88), calcium-channel blockers (24) or diuretics (229) did not reveal any clinically significant interactions with encainide. Similarly, in vitro protein binding studies did not reveal any clinically significant interactions with encainide or its major metabolites. Six patients with moderate to severe renal impairment (creatinine clearance 10 to 38 ml/min) received 25 mg of encainide, 3 times/day, for 7 doses. Plasma encainide, ODE and 3-methoxy-O-demethyl concentrations were similar to those observed in normal subjects who had received twice the dose of encainide, and steady-state apparent oral clearance of encainide was reduced by 66% with renal impairment. Based on these data it is recommended that in patients with moderate to severe renal impairment encainide be initiated at one-third the normal dose, or 25 mg once a day. Doses may be elevated in small increments at 1-week intervals if needed for efficacy. The effect of hepatic impairment on the pharmacokinetics of encainide was studied in 7 patients with clinically documented cirrhosis. Compared with normal subjects studied using a similar protocol, the plasma concentrations of encainide were elevated significantly due to a 6-fold decrease in oral clearance. Howeve

Topics: Adrenergic beta-Antagonists; Adult; Amiodarone; Anilides; Anti-Arrhythmia Agents; Anticoagulants; Antipsychotic Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cimetidine; Digoxin; Diuretics; Drug Interactions; Encainide; Humans; Hypoglycemic Agents; Kidney Diseases; Liver Diseases; Middle Aged; Prospective Studies; Protein Binding; Retrospective Studies

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Topics: Acute Kidney Injury; Adult; Antibodies; Bile; Bile Acids and Salts; Blood Proteins; Cardenolides; Chromatography, High Pressure Liquid; Digoxin; Female; Humans; Liver Diseases; Male; Middle Aged; Ouabain; Radioimmunoassay; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Adult; Aged; Digoxin; Female; Humans; Immunoassay; Kidney Failure, Chronic; Liver Diseases; Male; Middle Aged; Radioimmunoassay

We studied plasma digoxin levels by three methods in patients with congestive heart failure who had no, mild to moderate, and severe liver dysfunction secondary to the heart failure. Our results indicate that in patients with severe liver dysfunction, marked discrepancies in plasma can occur, depending on the methodology employed. The discrepancy is likely due to the presence of a digoxinlike immunoreactive substance.

Topics: Adult; Digoxin; Female; Heart Failure; Humans; Liver Diseases; Male; Middle Aged; Radioimmunoassay

Topics: Blood Proteins; Cardenolides; Digoxin; Fetal Blood; Humans; Kidney Diseases; Liver Diseases; Saponins

Topics: Adult; Aged; Bile Acids and Salts; Blood Proteins; Cardenolides; Digoxin; Female; Humans; Liver Diseases; Male; Middle Aged; Saponins

The Amersham Amerlex Radio-immunoassay was used to detect 'digoxin-like' substance in the sera of 37 elderly subjects, nine with renal impairment, 14 with hepatobiliary disease and 14 over-65-years-old controls with no renal or hepatic impairment. In the patients with hepatobiliary disease, digoxin-like substance was detected in 11 out of 14, the level being closely correlated with serum bilirubin (P less than 5.5 X 10(-10)) and significantly but less closely with serum alkaline phosphatase activity (P less than 10(-3)). While serum digoxin-like substance was detectable in seven out of nine patients with renal impairment, there was no correlation between the degree of renal impairment as reflected by blood urea and serum creatinine and serum digoxin-like activity. We suggest that in elderly subjects with renal impairment or hepatobiliary disease these findings should be borne in mind especially when considering digoxin toxicity.

Topics: Aged; Biliary Tract Diseases; Bilirubin; Digoxin; Humans; Kidney Diseases; Liver Diseases; Reference Values

Topics: Digoxin; Female; Humans; Liver Diseases; Pregnancy; Radioimmunoassay; Serum Albumin

Topics: Adult; Aged; Digoxin; False Positive Reactions; Female; Fluorescence Polarization; Humans; Liver Diseases; Male; Middle Aged; Radioimmunoassay

Topics: Digoxin; False Positive Reactions; Humans; Liver Diseases; Radioimmunoassay; Reagent Kits, Diagnostic

This method for assaying digoxin in serum with improved specificity combines small-column extraction of serum, "high-performance" liquid chromatography, and RIA of the eluted fractions. Analytical recoveries of 1.0, 0.5, and 0.1 microgram/L standards were 95%, 93%, and 84%, respectively. The CVs for duplicates and replicates of sera with values of 0.5 to 1 microgram/L were 4 to 6%. Fifty-nine sera from 50 patients receiving digoxin were so studied. All digoxin metabolites appear to cross react with antibody to digoxin to various degrees. The most polar metabolites were quantitatively the most important, their average cross reactivity being 33%. For eight patients the value for digoxin by the present method was less than 60% of the RIA value. Sera from nine patients not taking digoxin but with falsely high digoxin values were also studied by the present method. The digoxin peak was well resolved from those for (a) digoxin metabolites (except dihydrodigoxin), (b) digitalis-like factors in neonates and in patients with renal failure or combined hepatic and renal failure, and (c) two cross reacting drugs and their metabolites.

Topics: Adult; Chromatography, High Pressure Liquid; Cross Reactions; Digoxin; False Positive Reactions; Fetal Blood; Humans; Infant, Newborn; Kidney Failure, Chronic; Liver Diseases; Radioimmunoassay; Renal Dialysis

Immunoreactive digoxin was determined in blood samples of 73 patients with liver disease who did not take any cardiac glycoside. Seventeen of these patients reproducibly showed false-positive results, as much as 3.6 ng/ml. Patients with concomitant renal disease had higher assay results (mean 1.9 n/ml) than patients with normal renal function (mean 0.6 ng/ml). It is concluded that blood of a number of patients with liver disease of different causes contains a substance that interferes with digoxin radioimmunoassay.

Topics: Adult; Aged; Digoxin; False Positive Reactions; Female; Humans; Liver Diseases; Male; Middle Aged; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: Acute Kidney Injury; Blood Proteins; Cardenolides; Digoxin; Humans; Liver Diseases; Radioimmunoassay; Saponins

Topics: Acute Kidney Injury; Aged; Digoxin; Humans; Liver Diseases; Male

Topics: Anti-Inflammatory Agents; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Kidney Diseases; Liver Diseases

Topics: Chemical Phenomena; Chemistry; Digitalis; Digitoxin; Digoxin; Drug Interactions; Humans; Kidney Diseases; Kinetics; Liver Diseases; Plants, Medicinal; Plants, Toxic

Topics: Adrenergic beta-Antagonists; Digitalis Glycosides; Digitoxin; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Quinidine

Topics: Aged; Digitoxin; Digoxin; Humans; Kidney Diseases; Kidney Failure, Chronic; Liver Diseases

The effect of hepatic disease on the metabolism of drugs is reviewed. Drugs discussed include those acting on the central nervous system (phenobarbital, pentobarbital, amobarbital, diazepam, chlordiazepoxide, oxazepam, clorazepate, chlorpromazine, morphine, meperidine, phenytoin); those acting on the cardiopulmonary system (digoxin, digitoxin, lidocaine, theophylline); antineoplastic agents (azathioprine, 6-mercaptopurine, doxorubicin), antimicrobials (carbenicillin, ampicillin, nafcillin, chloramphenicol, clindamycin, lincomycin, rifampin, isoniazid, aminosalicylic acid) and antiinflammatory agents (phenylbutazone, prednisone). The effect of hepatic dysfunction on drug disposition is not consistent or predictable. The efficiency with which drugs are metabolized by the liver, the extent of drug plasma binding, and the etiology and stage of the hepatic disorder are each important in determining whether drug disposition will be altered.

Topics: Anti-Infective Agents; Antineoplastic Agents; Central Nervous System; Digoxin; Humans; Lidocaine; Liver Diseases; Pharmaceutical Preparations; Phenylbutazone; Prednisone; Theophylline

Topics: Biological Availability; Cardiac Glycosides; Creatinine; Deslanoside; Digitalis Glycosides; Digitoxin; Digoxin; Drug Interactions; Humans; Hypokalemia; Kidney Diseases; Liver Diseases; Malabsorption Syndromes; Obesity; Ouabain; Thyroid Diseases

Topics: Aged; Alcoholism; Allopurinol; Arrhythmias, Cardiac; Chloral Hydrate; Colchicine; Digoxin; Drug Synergism; Gastrointestinal Hemorrhage; Gout; Hospitals, Teaching; Humans; Liver Diseases; Male; Middle Aged; Nitroglycerin; Patient Care Team; Pharmacists; Pharmacy Service, Hospital; Quinidine; Warfarin; Washington

Topics: Adolescent; Aspartic Acid; Brain; Child; Child, Preschool; Clinical Enzyme Tests; Diagnosis, Differential; Digoxin; Electrocardiography; Erythrocytes; Female; Heart Diseases; Humans; Hydro-Lyases; Isomerases; Liver Diseases; Lyases; Male; Methandrostenolone; Muscular Diseases; Muscular Dystrophies; Oxidoreductases; Time Factors; Transferases; Vitamin E

Topics: Arteriovenous Fistula; Black People; Digoxin; Drug Therapy; Heart Failure; Hemangioendothelioma; Hemangioma; Hepatomegaly; Humans; Liver Diseases; Neoplasm Regression, Spontaneous

Topics: Arrhythmias, Cardiac; Clinical Laboratory Techniques; Digoxin; Female; Goiter; Graves Disease; Hepatomegaly; Humans; Hyperthyroidism; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodides; Liver Diseases; Maternal-Fetal Exchange; Prednisolone; Pregnancy; Pregnancy Complications; Reserpine; Splenomegaly; Thrombocytopenia; Toxicology; Vitamin K