digitoxin and Liver-Diseases

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: 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

To determine whether verapamil, diltiazem, or nifedipine affect digitoxin kinetics, glycoside plasma concentrations and renal excretion were measured before and during steady-state dosing in 30 patients with cardiac insufficiency. The mean (+/- SD) digitoxin plasma concentration was 14.27 +/- 3.66 ng/ml before and 18.15 +/- 5.33 ng/ml during verapamil dosing in 10 patients over a period of 4 to 6 weeks. Renal digitoxin clearance was not influenced by verapamil, but total body clearance and extrarenal clearance of digitoxin were reduced by 27% and 29%, respectively. Diltiazem resulted in a 6% to 31% (mean = 21%) increase in plasma digitoxin concentrations in five of 10 patients because of reduced extrarenal clearance of digitoxin. In contrast to verapamil, the concomitant dosing of nifedipine over 4 to 6 weeks did not alter digitoxin plasma levels or daily renal excretion. Based on these observations, the risk of digitalis intoxication after combined dosing with verapamil and digitoxin is much less pronounced than that after digoxin, and thus this glycoside is a valuable alternative.

Topics: Aged; Benzazepines; Clinical Trials as Topic; Digitoxin; Diltiazem; Drug Interactions; Drug Therapy, Combination; Female; Heart Diseases; Humans; Kidney; Kidney Diseases; Kinetics; Liver Diseases; Male; Middle Aged; Nifedipine; Radioimmunoassay; Verapamil

Traditional Chinese medicines are readily available without prescription from herbal drug stores. One such Chinese medicine, Chan Su, which is prepared from the skin gland of toads, has cardiotonic effect due to bufadienolides. Here we report rapid detection of the presence of Chan Su in blood using the fluorescence polarization immunoassay for digitoxin. In our study mice were fed with a dose of 75 mg/kg of Chan Su and blood was drawn before, and 1 and 2 h after feeding. We observed significant digitoxin-like immunoreactivity in the sera. For example in one mouse the digitoxin-like immunoreactivity was undetectable before feeding with Chan Su, but was 19.7 ng/ml 1 h and 8.8 ng/ml 2 h afterwards. The apparent half-life of Chan Su is approximately 1 h in mice. In another experiment, we studied protein binding of Chan Su by measuring total and free Chan Su concentrations (ultrafiltrate prepared by using Centrifree Micropartition Filter, molecular weight cutoff: 30000 Da). Chan Su was strongly bound to serum proteins. We observed higher free fraction in uremic sera and sera from patients with liver disease. We identified albumin as one of the proteins that bind Chan Su in serum.

Topics: Animals; Bufanolides; Digitoxin; Liver Diseases; Mice; Uremia

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

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

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

Topics: Administration, Oral; Arrhythmias, Cardiac; Biological Availability; Digitoxin; Dosage Forms; Humans; Immunoenzyme Techniques; Kidney Diseases; Liver Diseases; Radioimmunoassay; Specimen Handling

Topics: Digitalis; Heart Diseases; Humans; Lanatosides; Liver Diseases; Liver Diseases, Alcoholic; Plants, Medicinal; Plants, Toxic; Time Factors; Virus Diseases

Following administration of digitoxin, 1 mg intravenously, the pharmacokinetics of this glycoside were studied in eight healthy volunteers and in eight patients with hepatorenal insufficiency (mean creatinine clearance 19.6 +/- 2.9 ml/min; antipyrine clearance 25.6 +/- 3.2 ml/min; means +/- SEM). Liver cirrhosis of the patients was confirmed by liver biopsy. Plasma protein binding of digitoxin (means +/- SEM) was 95.1 +/- 0.7% in the patients and 95.6 +/- 1.2% in the volunteers (NS). Total body clearance of digitoxin was 0.0530 +/- 0.0040 ml/min/kg of body weight in the patients and 0.0547 +/- 0.0043 ml/min/kg of body weight in the healthy subjects (NS). When elimination half-lives of the patients and the volunteers were compared, there was also no significant difference (7.0 +/- 0.77 days in the patient group and 7.8 +/- 0.8 days in the volunteers). Our data concerning digitoxin kinetics in patients with hepatorenal insufficiency do not indicate an accumulation of the drug in these patients.

Topics: Adult; Aged; Biological Availability; Body Weight; Digitoxin; Female; Half-Life; Humans; Kidney Diseases; Kinetics; Liver Diseases; Male; Middle Aged

Serum digitoxin levels were measured during maintenance treatment with digitoxin, 0.1 mg daily i.v., in 12 patients under intensive postoperative care who had hepatorenal failure resulting from multiple organ failure. Thirteen patients in intensive care with comparable basic diseases served as controls; they had developed predominantly renal failure. Serum digitoxin levels in the two groups were no different and remained within therapeutic range during the total period of observation of 8-40 days. During this time toxic serum digitoxin levels were measured in 2.9% of patients in renal failure and 2.7% of patients with hepatorenal failure. The pathogenesis of the liver failure and the severity of the underlying disease did not influence serum digitoxin levels. Digitoxin was tolerated similarly in the two patient groups.

Topics: Adult; Aged; Digitoxin; Female; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Shock; Shock, Septic

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

Topics: Animals; Barbiturates; Bile Acids and Salts; Biotransformation; Bisacodyl; Chloramphenicol; Cholestasis; Digitoxin; Enterohepatic Circulation; Humans; Liver Cirrhosis; Liver Diseases; Neomycin; Phenytoin; Rats; Spironolactone

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: Digitoxin; Humans; Liver Diseases; Metabolic Clearance Rate

Topics: Adolescent; Adult; Aged; Blood Urea Nitrogen; Creatinine; Digitoxin; Feces; Female; Humans; Kidney Failure, Chronic; Liver Diseases; Male; Middle Aged; Tritium