digoxin and Malabsorption-Syndromes

The absorption of oral digoxin preparations has been a topic of much concern during the last 5 years. The completeness of digoxin absorption is proportional to the area under the serum concentration time curve and to the urinary excretion of digoxin after single doses. During chronic therapy the completeness of absorption is proportional to these values and also to the steady state serum concentration. Determination of absolute bioavailability of a given digoxin preparation requires a comparative study using intravenous digoxin as a standard. Oral digoxin solutions are incompletely absorbed, but have biological availability greater than or equal to that of tablets. The absorption of digoxin tablets depends upon their dissolution rate which in turn is related to drug particle size. Digoxin tablets with small drug particles have rapid rates of dissolution and can be absorbed as completely as oral solutions. The bioavailability of digoxin from tablets can be influenced by changes in gastro-intestinal motility, malabsorption syndromes, and by co-administration of food or other drugs. New regulations now insure that all marketed digoxin tablet preparations have satisfactory bioavailability. Problems with biological availability at present are unlikely to account for unexpected clinical results during digoxin therapy.

Topics: Biological Availability; Digoxin; Drug Interactions; Food; Gastrointestinal Motility; Humans; Injections, Intramuscular; Intestinal Absorption; Malabsorption Syndromes; Mathematics; Models, Biological; Pharmaceutical Preparations; Solutions; Tablets; Time Factors

Antibodies to digitalis glycosides have been elicited in experimental animals and have been utilized in the development of rapid, sensitive, specific and convenient radioimmunoassay methods for the clinical measurement of digoxin and other cardiac glycosides in man. The use of these assay methods has supplemented earlier studies with radiolabeled digitalis preparations and has made it possible to obtain much new information concerning factors which may contribute to the well known patient to patient variability in digitalis dosage requirements and in sensitivity to the toxic effects of cardiac glycosides. In some patients with a poor clinical response to digitalis, the finding of a serum concentration which is relatively low for the dose prescribed may suggest that true digitalis resistance is not present and may raise questions of poor patient compliance, tablet inadequacies, intestinal malabsorption, increased metabolic degradation or hyperthyroidism; if the cause of the low serum level cannot be identified or corrected, serial serum measurements should enable safe and rational upward adjustment of dosage. In some patients with digitalis toxicity, the finding of a serum level which is relativity high for the dose prescribed may suggest that the patient is not sensitive to digitalis but rather is excreting it slowly; in such instances in elderly patients (with decreased glomerular filtration rates) and in patients with renal disease, serial digitalis measurements are useful adjuncts to clinical observation in determining optimal digitalis dosage schedules. A knowledge of serum digitalis concentrations should enable us to develop sound principles for a more rational approach to the clinical administration of cardiac glycosides, especially in patients with unusually high dosage requirements or with unusual sensitivity to relatively small doses of digitalis.

Topics: Animals; Antibodies; Antibodies, Anti-Idiotypic; Arrhythmias, Cardiac; Biological Availability; Cardiomyopathies; Cattle; Cooperative Behavior; Digitalis Glycosides; Digoxin; Drug Interactions; Drug Resistance; Humans; Infant; Intestinal Absorption; Malabsorption Syndromes; Radioimmunoassay; Tablets; Tachycardia; Tritium

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: Biopharmaceutics; Capsules; Digoxin; Drug Interactions; Food; Half-Life; Humans; Intestinal Absorption; Malabsorption Syndromes; Neomycin; Radioimmunoassay; Tablets; Time Factors

The relative steady-state bioavailability of two oral digoxin dosage forms was studied in 17 subjects with malabsorption syndromes. Male subjects received the following treatments in randomized crossover fashion for 14 days: three 0.125-mg digoxin tablets or three 0.1-mg digoxin capsules once daily. Female subjects received digoxin on the same schedule but at two-thirds the dose. Serum and urine samples were collected and analyzed for digoxin by radioimmunoassay, and treatments were compared by evaluating pharmacokinetic parameters. The mean area under the serum concentration versus time curve for tablets (28.1 h.nmol/L [21.9 h.ng/mL]) was smaller (p less than 0.03) than that for capsules (31.1 h.nmol/L [24.3 h.ng/mL]), and the mean maximum serum digoxin concentration for tablets (2.9 nmol/L [2.3 ng/mL]) was lower (p less than 0.02) than that for capsules (4.0 nmol/L [3.1 ng/mL]). There was no difference in cumulative urinary excretion of digoxin between the two treatments. In contrast to previous reports, we observed that digoxin from Lanoxin Tablets appears to be well absorbed in subjects with malabsorption. Nevertheless, these subjects absorbed digoxin from capsules better than from tablets, with the greatest differences occurring in subjects without a colon and in those subjects with the lowest serum carotene concentrations.

Topics: Adult; Aged; Capsules; Digoxin; Female; Humans; Malabsorption Syndromes; Male; Middle Aged; Tablets

To report a case of malabsorption of digoxin from tablets, gel caps, and elixir in a patient with an end jejunostomy.. A 69-year-old man with 18 cm of functioning jejunum following a surgical end jejunostomy was receiving oral digoxin. The patient presented on referral for short bowel syndrome, secretory diarrhea, and malabsorption. He was receiving digoxin tablets 0.75 mg/d with a serum digoxin concentration of 0.5 ng/mL. Attempts to achieve therapeutic digoxin serum concentrations of approximately 1.0 ng/mL by administration of digoxin in the form of liquid-filled gel caps and elixir were unsuccessful.. Variable results have been presented in the literature regarding the ability to achieve therapeutic concentrations of digoxin following oral administration in patients with malabsorption syndromes. Several studies have suggested that changing the form of administered digoxin from tablet to elixir or liquid-filled gel caps may improve absorption in patients with small intestine malabsorption. Such changes in oral dosage form failed to achieve therapeutic digoxin serum concentrations in this case.. The markedly diminished length and the lack of continuity of this patient's small intestine and colon likely resulted in severe malabsorption of orally administered digoxin. Some patients with end jejunostomies may require intravenous forms of medication because of inadequate absorption of orally administered medications.

Topics: Administration, Oral; Aged; Capsules; Digoxin; Humans; Jejunostomy; Malabsorption Syndromes; Male; Pharmaceutical Vehicles; Short Bowel Syndrome; Tablets

Topics: Aged; Digoxin; Female; Humans; Intestinal Absorption; Malabsorption Syndromes; Short Bowel Syndrome

Topics: Antineoplastic Agents; Digoxin; Drug Interactions; Humans; Intestinal Absorption; Lymphoma; Malabsorption Syndromes; Time Factors

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

Gastro-intestinal absorption of digoxin was evaluated in 18 patients with progressive systemic sclerosis. In 8 patients a single-dose crossover study was performed after oral and intravenous administration of 0.5 mg digoxin by comparing the aera under the eight-hour plasma concentration curve. The fraction of the dose absorbed was diminished in 4 patients to less than 55%. There was a significant positive correlation between the extent of digoxin absorption and xylose renal excretion. In addition, steady state digoxin plasma levels and 24-h urinary excretion of digoxin were determined during maintenance therapy in 12 patients. In 6 patients renal excretion of digoxin was clearly less than in normal subjects during chronic dosing of the same digoxin preparation. This finding corresponded well with digoxin plasma levels below the usual therapeutic range in most of the patients. The impaired absorption of digoxin failed to correlate with the extent of the skin manifestation or the time course of the disease while there was massive oesophageal dysfunction in most of these patients. The results suggest that an inadequate therapeutic response to cardiac glycosides in patients suffering from progressive systemic sclerosis is at least partially due to impaired digoxin absorption. Similar problems could occur in therapy of the disease itself due to insufficient enteral absorption of drugs used in treatment of systemic sclerosis.

Topics: Administration, Oral; Adult; Biological Availability; Digoxin; Female; Humans; Injections, Intravenous; Intestinal Absorption; Intestine, Small; Malabsorption Syndromes; Male; Middle Aged; Scleroderma, Systemic; Xylose

Topics: Celiac Disease; Digoxin; Humans; Hyperthyroidism; Malabsorption Syndromes

Topics: Administration, Oral; Adult; Biological Availability; Carcinoma, Squamous Cell; Digoxin; Female; Heart Failure; Humans; Injections, Intramuscular; Intestinal Absorption; Malabsorption Syndromes; Radiotherapy; Solutions; Tablets; Uterine Cervical Neoplasms

Topics: Chromatography, Thin Layer; Digoxin; Dosage Forms; Feces; Humans; Intestinal Absorption; Malabsorption Syndromes; Tablets; Tritium

Topics: Administration, Oral; Blood Proteins; Body Weight; Calcium; Celiac Disease; Digoxin; Feces; Humans; Intestinal Absorption; Lipids; Magnesium; Malabsorption Syndromes; Pancreatic Diseases; Xylose

Topics: Digitalis Glycosides; Digitoxin; Digoxin; Humans; Intestinal Absorption; Malabsorption Syndromes