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Measurement was made of digoxin particle size in three brands of digoxin powder used for tablet manufacture. The geometric mean particle diameters were 20, 22 and 29 µm. When the 22 µm powder was administered within a cachet absorption of the digoxin occurred slowly and low steady state levels were obtained. Ball milling of the 22 µm powder was used to produce powders of mean diameters 12 and 3.7 µm. These powders produced more rapid and more complete absorption of the digoxin. The results indicate that particle size is a major factor in the biological availability of digoxin formulations. [ABSTRACT FROM AUTHOR]

The metabolites of tritiated 4‴-methyldigoxin (MD) has been studied in bile, urine and faeces from 3 patients 24 h after cholecystectomy and T-tube drainage. 5.6-15.6% of the doses were eliminated in bile and 28.5-57.8% in urine within 48 h. In bile after 6 h, approximately 5% of the excreted products were bisglycosides (B) and only traces were monoglycosides (M), whereas 55.3±4.5% were CHCl-insoluble metabolites. At the same time urine contained 15.5±1.3% CHCl-insoluble compounds. Anaerobic incubation of bile with a stool suspension (SS) decreased the polar fraction by 64.8±4.5% (n=6); incubation with a previously autoclaved SS decreased it only by 12.7±2.7%. Preincubation of SS with carbenicillin, cephalotin and ampicillin to depress bacterial growth largely suppressed the metabolic activity. TLC-analysis revealed that the decrease in the polar fraction corresponded to an increase of M, whilst MD, digoxin and B were almost unaltered. The results imply that B and M were formed in the liver, B was preferentially eliminated unchanged in bile and M was conjugated to CHCl-insoluble compounds prior to excretion. The polar conjugates were split by bacterial enzymes in the colon to yield M, which could be detected in faeces. [ABSTRACT FROM AUTHOR]

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Focuses on a study which tested the bioavailability of four lots of digoxin tablets with different dissolution rates. Subjects and method; Results; Discussion.

Presents a study which monitored adverse reactions to digoxin in hospitalized medical patients in a drug surveillance program in Boston, Massachusetts. Comparison of the correlation of the intensity of action of most drugs with their concentration in the serum and their dosage; Frequency of adverse reactions to digoxin in hospitals monitored by the drug surveillance program; Effectiveness of measuring serum drug concentrations in reducing the frequency of adverse drug reactions.

Serum digoxin levels in nontoxic patients obtained 6 to 24 hours after administration of a maintenance dose of digoxin were measured by means of a radioimmunoassay method. There were 31 infants, 33 children, and 24 adults studied; 19 digitalis-toxic patients were also investigated. The mean serum digoxin concentration in the nontoxic infants was 2.8 (± 1.9) ng/ml, a level significantly greater than that obtained in the older children or adults, 1.3 (± 0.4) ng/ml and 1.3 (± 0.6) ng/ml, respectively (P < .01). In the infant group, similar dosage schedules resulted in a higher serum concentration when the digoxin was administered intramuscularly rather than orally, but differences were also related to the age of the patients within the infant group. Sixty-five percent of the infants receiving standard maintenance therapy had digoxin levels > 2.0 ng/ml, a range which is commonly associated with toxicity in adults, whereas only 18% of the children had serum concentrations above this value. Mean serum digoxin levels in the digitalis toxic infants was 4.4 ng/ml and in the toxic children 3.4 ng/ml. Eleven of these 15 patients had received digoxin intramuscularly. The mean serum level measured in digitalis-toxic adults was 2.9 ng/ml. Serum digoxin levels may be of value (1) as an adjunct in the diagnosis of toxicity, (2) in the early evaluation of accidental ingestion, (3) in the assessment of the adequacy of digitalization, and (4) in the management of digitalization of patients with renal insufficiency. [ABSTRACT FROM AUTHOR]

The absorption, tissue concentration, and urinary and fecal excretion of ³H-digoxin was studied in 20 infants with serious congenital cardiac malformations and, except for minor differences, the results were in the same range as those reported for adults. The published recommendations of higher dosage requirements in infants for maximum therapeutic effectiveness and the suggested lower dosage for the neonatal period to reduce the danger of toxicity can therefore not be explained by differences in absorption, tissue fixation, and excretion of the glycoside by the neonate and infant when compared with the adult. A major difference is that infants excrete primarily unchanged digoxin, whereas adults excrete both unaltered digoxin and metabolites. [ABSTRACT FROM AUTHOR]

The kinetics of absorption, of changes in blood concentration, and of biliary excretion after the i.v. and i.d. administration of 40 μCi each, of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin were studied in biliary fistula rats. The highest blood concentrations were found after the i.v. administration of 4‴-methyldigoxin, which decline with a half life time of 10 h, compared with 5.6 and 4.5 h for 4‴-acetyldigoxin and digoxin respectively. 71%, 55% and 17% of the dose were excreted in the bile within 12 h after the i.v. administration of digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin. The blood concentrations observed after the i.d. administration of digoxin and 4‴-acetyldigoxin show almost identical pharmacokinetics with respect to height and elimination velocity (half life 7.0 h for digoxin and 7.5 h for 4‴-acetyldigoxin). In contrast, following the i.d.administration of 4‴-methyldigoxin, blood concentrations, which were twice as high, were observed and declined with the same half life as after the i.v. administration. Determination of the disappearance rates of these glycosides from the intestinal lumen reveals a biphasic course of absorption. A first phase, with k values of 0.4, 0.5, 1.2 for digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin respectively is followed by a second phase with k values of 0.04, 0.04, 0.001 for digoxin, 4‴-acetyldigoxin and 4‴-methyldigoxin. Thus, 4‴-methyldigoxin is almost completely absorbed within the first two hours, while digoxin and 4‴-acetyldigoxin continue to be absorbed during the following hours. The absorption velocity of digoxin from the ileum was found to be one half of that seen in the duodenum. But this slow absorption, as well, follows a biphasic course. The data indicate that 4‴-methyldigoxin is absorbed at a distinctly higher rate than 4‴-acetyldigoxin and digoxin. Acetylation in 4‴ position evidently provides no important advantage with respect to absorption. While this study allows the determination of absorption and excretion velocities, no account of absorption quotes is given. [ABSTRACT FROM AUTHOR]

In man the oral or intravenous administration of 4‴-methyldigoxin yields metabolites in urine which are soluble either in chloroform or in water. The chromatographic analysis reveals demethylation as the main metabolic reaction in man. In addition to methyldigoxin and digoxin small amounts of digoxigenin-bisdigitoxoside and digoxigenin-mono-digitoxoside can be detected. The water soluble metabolites represent 7% of the radioactivity excreted in 7 days reaching a maximum within the first 8 h. [ABSTRACT FROM AUTHOR]

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, , 448-452. Thirty-seven children with transposition of the great arteries have undergone Mustard's operation in Birmingham Children's Hospital from May 1968 to December 1971. Thirtythree of these had simple transposition of the great arteries and four were complicated. All but two had some previous palliative procedures. Ten patients died before discharge from hospital and there were two late deaths, one after three months and the other after eight months. Bleeding, dysrhythmia, and hypotension were common immediate postoperative complications, while recurrent heart failure and persistent atrioventricular block occurred in five and four patients respectively. [ABSTRACT FROM PUBLISHER]

Discusses the pharmacokinetics of digitalis glycosides. Types of cardiac glycosides; Absorption, metabolism and excretion of digoxin; Major difference between digoxin and metabolite digoxin; Special problems of therapy.

Presents abstracts of scientific papers about internal medicine. 'Correlation of Serum Digoxin Level With Acetylstrophanthldin Tolerance,' by I. Barr; 'Vascular Lesions Associated With Use of Oral Contraceptives,' by Ancel Blaustein; 'Phasic Renal Artery Blood Flow Velocity in Men During Cardiac Arrhytmias,' by Alberto Benchimol.

Presents abstracts of articles published in the April 1970 issue of the "Annals of Internal Medicine". "Serial blood gas studies during cardiopulmonary resuscitation"; Transient cerebral ischemia due to arrhythmia"; An improved method of digitoxin therapy"; "Alternate-day steroid therapy in lupus nephritis".

An improved method of digitoxin therapy is presented for adult euthyroid patients of average weight with normal hepatic function, electrolyte balance, and gastrointestinal absorption whose renal function may be normal, reduced, or changing. The method uses a loading dose of 0.8 to 1.4 mg of United States Pharmacopeia (USP) digitoxin in three divided doses 6 hr apart. The proper maintenance dose depends on renal function. Reasonable estimates of it are found from graphs and simple equations presented. In 95% of patients the maintenance dose should sustain body glycoside stores at 73 to 150% of the selected level when renal function is normal and from 73 to 133% in anuric patients. Caution is urged when raising body glycoside stores above 1.4 mg, though this may be necessary to control ventricular rate when atrial arrhythmias are present. [ABSTRACT FROM AUTHOR]

Focuses on a study which evaluated a method of oral digoxin therapy for euthyroid patients with normal electrolytes and gastrointestinal absorption. Digoxin kinetics in patients; Effects of reduced renal function on digoxin kinetics; Kinetics of accumulation without a loading dose.

Presents information on a study which analyzed the metabolism of digoxin in patients undergoing hemodialysis and peritoneal dialysis. Results of in vitro hemodialysis performed; Peritoneal clearance rate of tritiated digoxin; Results of the experiment comparing the dialysis of digoxin from saline and from serum.

Focuses on tissue distribution and the concentration of tritiated digoxin in human subjects. Relationship between the level of blood urea nitrogen and digoxin excretion; Illustration of the tissue/serum ratio at the time of death; Comparison between the myocardial concentration and serum concentration of digoxin; Effect of the concentration of digoxin on several parts of the body.

Provides information on a study which examined whether there were objective differences in tritiated digoxin blood levels among patients with hypo- and hyperthyroidism. Development of thyroid disease; Tests conducted on the serum levels and excretion of digoxin; Discussion of the administration of digoxin.

PST is a life-threatening medical emergency, and the pediatrician should be aware of its signs and symptoms. Digoxin is very effective in terminating PST and relieving the cardiac failure which is usually present-especially when the attack has lasted 24 hours or longer. Prophylactic medication with either Digoxin or quinidine sulfate is of questionable value. It is best to treat each recurrence as if it were an initial episode of PST. [ABSTRACT FROM AUTHOR]

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Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

H-digoxin andH-digitoxin were given orally to two middle-aged women who had thoracic duct lymphatic drainage. The plasma levels and urinary excretion of radioactivity were essentially the same as in normal controls. The cumulative recovery ofH-digoxin and its metabolites in lymph collected for 3 days was 4 per cent; and the corresponding value after administration ofH-digitoxin was 20 per cent. It was concluded that only minor amounts of digoxin and digitoxin are absorbed through lymphatic pathways. [ABSTRACT FROM AUTHOR]

The protein binding of digoxin in human serum was investigated using equilibrium dialysis and tritium-labelled digoxin. A constant protein bound fraction of about 30% was found over a wide range of concentrations of digoxin including therapeutic levels. Interpretation of the findings according to the law of mass-action showed an association constant K = 0.68·10l/mol; and, the number of binding sites, n → ∞, indicating an almost infinite apparent maximum binding capacity and a very small affinity of human serum proteins for digoxin. [ABSTRACT FROM AUTHOR]

Editorial. Emphasizes the clinical significance of the drug digitalis serum. Physiological implications of digitalis serum levels; Technique in measuring digitalis serum levels; Relationship between digoxin serum concentration and myocardial concentration of the drug.

Aim. To compare effectiveness of carvedilol as monotherapy and in combination with digoxin for heart rate (HR) control in patients with persistent atrial fibrillation (AF) and chronic heart failure (CHF). Material and methods. In total, 45 men and women, aged 42-77 years, with persistent AF and NYHA Functional Class II-III CHF were randomized into two treatment groups, and sub-divided by baseline ejection fraction, EF (EF>45%; EF45%, non-significant benefits of carvedilol monotherapy were registered. Conclusion. In CFH patients with persistent AF and baseline EF>45%, carvedilol monotherapy was more effective; in EF>45%, combined therapy had more clinical benefits. Moreover, combined therapy was more effective in baseline HRMOO, and carvedilol monotherapy - in baseline HR

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)