Digoxin Blood Levels Research Articles

Transient Cardiac Rhythm Changes.

Scenario: The 2 rhythm strips shown here (approximately 18 minutes apart) are from a 76-year-old woman admitted to the cardiac telemetry unit for exacerbation of heart failure. The patient’s history includes hypertension, type 2 diabetes, diastolic heart failure due to long-standing hypertension, and an atrioventricular (AV) pacemaker. The patient is resting comfortably in bed and is scheduled for discharge in the late afternoon. Given the rhythm strips, is it safe to discharge the patient?Normal sinus rhythm with possible right atrial enlargement and secondary repolarization changes. There is intermittent AV paced rhythm with appropriate AV sensing and pacing.A 3-letter code is used to describe the type of pacing used. The first letter denotes the chamber paced: A = atrium, V = ventricle, D = dual (ie, both A and V). The second letter denotes the chamber sensed, using the same nomenclature. Sensing inhibits pacing when an intrinsic P wave and/or QRS complex is present. The third letter denotes the response to sensing: I = inhibit, T = triggered, and D = dual function. In the top electrocardiography (ECG) strip, atrial activity is sensed (consistent P waves); thus, atrial pacing is inhibited. However, after the seventh P wave, an intrinsic QRS complex does not occur for >22 milliseconds, which triggers ventricular pacing. In the bottom strip, just after the ventricular paced beat, a P wave is not sensed and atrial pacing occurs. However, an intrinsic QRS complex occurs after atrial pacing, thus inhibiting ventricular pacing. By the sixth beat, both P waves and QRS complexes are sensed, thus inhibiting both atrial and ventricular pacing. This pattern suggests that the patient’s pacemaker is DDD. Moreover, the asymmetric biphasic P waves suggest atrial enlargement. Given that the impulse propagates from right to left atrium, a larger initial P compared with the terminal P’ suggests that the right chamber is the one enlarged. The T-wave inversion in lead II is most likely secondary repolarization changes due to diastolic dysfunction and right ventricular hypertrophy (cor pulmonale), consistent with the patient’s history. Verify with a 12-lead ECG and/or echocardiogram if available.The development of the first-degree AV block is the reason that transient pacing occurs. Medications (ie, β-blockers and/or digoxin) are a potential source of the problem, so medications in use should be evaluated as a possible cause and adjusted accordingly. Digoxin blood levels would be helpful; however, this patient is not taking digoxin. This patient’s DDD pacer is functioning properly; hence, no intervention is necessary and the patient can be discharged home.

Enzalutamide and analytical interferences in digoxin assays

Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide.Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis.Methods: The second patient’s digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule.Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient’s plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method.Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

Proton Pump Inhibitor-Induced Leak Across Gastric Mucosa: Effect of H-2 Blockers

Previous patient-based studies by our group have shown that the proton pump inhibitor, esomeprazole, induces a transmural leak in gastric mucosa (Mullin et al., Alimentary Pharmacology and Therapeutics, 28(11-12): 1317-25, 2008). Subsequent studies by our group using rat gastric corpus mucosa showed that this leak is bidirectional, has an upper size limit of 10 kDa, and is a class effect for PPIs in general, holding true for omeprazole and lansoprazole as well as esomeprazole. Additionally, we have demonstrated that the small molecule drug, digoxin, is capable of passing through this leak, with the potential of thereby elevating digoxin blood levels above their therapeutic target. In this current study we asked whether the H-2 blocker, famotidine, would have a similar effect to PPIs. Test subjects performed an initial (baseline) sucrose permeability test just prior to beginning medication. Subjects then took a daily (morning) dose of famotidine (40 mg) or omeprazole (20 mg) for 5 days. On the evening of the 5th (last) day, subjects performed a second sucrose permeability test. Subjects taking omeprazole for 5 days (n = 10) manifested a 5-fold increase in sucrose leak. Subjects taking famotidine for 5 days (n = 10) manifested only a 15% increase in leak, which was not statistically significant (P = 0.54, Student's t test). The increased leak of subjects on omeprazole was highly significant (P<0.0005). These findings support the hypothesis that induction of transmucosal gastric leak is not simply a function of inhibition of acid secretion, but instead is a property more specific to PPIs per se. Future studies will however test whether longer duration exposure to famotidine can induce leak, or whether a famotidine-induced leak disappears in 12-24 hrs after a 40 mg oral dose. This work was supported by funding from the Sharpe/Strumia Foundation.

Common ATP-binding cassette B1 variants are associated with increased digoxin serum concentration

Digoxin is a known substrate of ATP-binding cassette B1 (ABCB1/MDR1). The results of studies on the association between ABCB1 polymorphisms and digoxin kinetics, however, remain contradictory. Almost all studies were small and involved only single dose kinetics. The goal of this study was to establish ABCB1 genotype effect on digoxin blood concentrations in a large cohort of chronic digoxin users in a general Dutch European population. Digoxin users were identified in the Rotterdam Study, a prospective population-based cohort study of individuals aged 55 years and above. Digoxin blood levels were gathered from regional hospitals and laboratories. ABCB1 single nucleotide polymorphisms (SNPs) 1236C-->T, 2677G-->T/A, and 3435C-->T were assessed on peripheral blood DNA using Taqman assays. We studied the association between the ABCB1 genotypes and haplotypes, and digoxin blood levels using linear regression models adjusting for potential confounders. Digoxin serum levels and DNA were available for 195 participants (56.4% women, mean age 79.4 years). All three ABCB1 variants were significantly associated with serum digoxin concentration (0.18-0.21 microg/l per additional T allele). The association was even stronger for the 1236-2677-3435 TTT haplotype allele [0.26 mug/l (95% CI 0.14-0.38)], but absent for other haplotypes (CGC allele considered referent), suggesting an interaction of SNPs in a causal haplotype instead of individual SNP effects. We found that the common ABCB1 1236C-->T, 2677G-->T, and 3435C-->T variants and the associated TTT haplotype were associated with higher digoxin serum concentrations in a cohort of elderly European digoxin users in the general population.

Niveles inapropiados de digoxina en sangre relativos a 2.849 pacientes procedentes de un hospital universitario: influencia de la edad y el sexo

Digoxin is used to treat congestive heart failure and atrial fibrillation. Blood levels need to be monitored to optimize therapeutic performance, detect noncompliance and reduce toxicity. The aim of this study was to evaluate the use of digoxin by measuring blood levels of this drug. The influence of sex and age were also considered. A retrospective study reviewed determinations of blood digoxin concentration in hospitalized and ambulatory patients with congestive heart failure, atrial fibrillation, or both, seen at the University of Granada Teaching Hospital (Spain) from 1992 to 2002. A chi square test was applied to results. A total of 5,623 laboratory tests for digoxin were done for 2,849 adult patients. Patients whose medical record was incomplete were excluded, and the final sample consisted of 2,629 patients. The 55.4% had inappropriate blood levels of digoxin. Inappropriate concentrations to digoxin were significantly higher in women (p < 0.001). The percentage of patients with high levels of the drug was significantly greater among men (p < 0.001). Very low concentrations (< 0.5 ng/ml) were found in 16% of the patients, with no significant difference between sexes. We detect a large percentage of older patients with inappropriate levels of digoxin in blood. Women were more likely than men to have high levels to digoxin in blood. There is evidence that therapeutic monitoring of blood levels of digoxin is not done as often as is advisable; this has implications for the care of patients being treated with this drug.

Digoxin visual toxicity with therapeutic blood levels of digoxin

To report two cases of digoxin-related visual disturbances associated with therapeutic blood levels of digoxin. Case reports. One patient reported shimmering lights in the field of vision of both eyes; the second patient had a corrected visual acuity of BE, 20/40 and generalized visual field depression in both eyes. Both patients experienced these symptoms while receiving digoxin. Both patients had digoxin blood levels in the therapeutic range (1.7 and 1.0 ng/ml, respectively). Therapeutic levels are 0.5 to 2.0 ng/ml. After discontinuing digoxin, the first patient noted that the shimmering light symptoms resolved, and the second patient had improved visual acuity and visual fields. Digoxin-related visual toxicity may be associated with therapeutic blood levels of digoxin. Recognition of this entity may avoid unnecessary testing and frustration.

Intravenous amiodarone in treatment of recent-onset atrial fibrillation: Results of a randomized, controlled study

This study was designed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation. The optimal approach for acute atrial fibrillation has not been established. Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias, but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated. Sample size was calculated to detect a 25% increase in reversion rate with amiodarone with a statistical power of 80%. One hundred consecutive patients with recent-onset (<1 week) atrial fibrillation and not taking antiarrhythmic agents were randomized to receive either intravenous amiodarone, 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h, or an identical amount of saline. Both groups received intravenous digoxin, 0.5 mg initially, followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter, to complete 24 h while the ventricular rate was >100 beats/min. Amiodarone and digoxin blood levels were determined. Both groups were homogeneous regarding underlying heart disease, time from onset to treatment, initial ventricular rate and left atrial size. By the end of the 24-h treatment period, 34 patients (68%, 95% confidence interval [CI] 53% to 80%) in the amiodarone group and 30 (60%, 95% CI 45% to 74%) in the control group had returned to sinus rhythm (p = 0.532). Mean times (+/-SD) of conversion were 328 +/- 335 and 332 +/- 359 min, respectively (p =0.957). Among patients who did not convert to sinus rhythm, treatment with amiodarone was associated with a slower ventricular rate (82 +/- 15 beats/min in the amiodarone group vs. 91 +/- 23 beats/min in the control group, p = 0.022). After restoration of sinus rhythm, atrial fibrillation recurred during a 15-day follow-up period in 4 (12%) of 34 patients (95% CI 3% to 27%) in the amiodarone group and in 3 (10%) of 30 (95% CI 2% to 26%) in the control group (p = 0.861). Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm.

Serum Digoxin Levels Related to Plasma Propafenone Levels During Concomitant Treatment

Nine patients with supraventricular rhythm disorders were treated during 5-day periods with different oral doses (300, 450, 600, and 900 mg daily) of propafenone concomitantly to long-term digoxin treatment. A poor correlation (r = .398; P less than .05) was obtained when the difference between the mean digoxin serum level (calculated with the Cmin data determined each of the 5 days) observed during a given propafenone dose and the mean digoxin serum level observed before propafenone treatment, was correlated with the dose of propafenone; but an evident correlation (r = .778; P less than .01) was found when the difference in digoxin level was correlated with the plasma propafenone concentration. The propafenone effect of increasing digoxin blood levels was thus concluded to be poorly dose dependent but strongly concentration dependent. The association of propafenone to a long-term digoxin treatment can be considered with a low risk of toxicity when plasma propafenone concentration does not exceed about 1000 ng/mL. Propafenone plasma levels are unpredictable in view of their wide interindividual variation for a given dose, so their measurement is advised to detect high levels and consequently to prevent a rise in digoxin serum concentrations with the possibility of toxicity. In clinical practice, when propafenone concentration determinations are not readily available, digoxin serum levels at least have to be carefully monitored.

健常人におけるジゴキシン血中濃度の変動から見たジゴキシン０．１２５ｍｇ錠の有用性

健常人におけるジゴキシン血中濃度の変動から見たジゴキシン０．１２５ｍｇ錠の有用性

Dose of digoxin and age of child.

A single dose study was carried out to compare blood levels of digoxin using three preparations marketed as syrup and tablets. Digoxin was estimated by radio-immunoassay. Although blood levels at two and four hours did not reveal any difference in bioavailability of the three products, the levels varied to a great extent in children of different age groups. Children below six years of age, who were given digoxin in the dose of 0·025 mg/kg/day showed higher mean concentration (1·62±0·18 ng/ml) as compared with (0·98±0·45 ng/ml) children of 6 to 12 years age group, who were given digoxin in the dose of 0·25 mg/day. These doses calculated according to body weight had a mean value of 0·01 mg/kg/day. It is suggested that children above the age of six years be also given digoxin on a dose per weight basis to maintain adequate levels.

Mexiletine: Its Role in the Management of Chronic Ventricular Arrhythmias

Mexiletine is a class IB anti arrhythmic agent structurally similar to lidocaine but with the advantage of a high bioavailability and relatively long half‐life, making it useful for long‐term oral therapy of ventricular arrhythmias. Mexiletine can be used orally or intravenously. Orally, it has a high bioavailability, reaching peak plasma concentration between 2 and 4 hours after administration. The steady‐state therapeutic plasma concentration ranges from 0.5 to 2.5 fig/ml. These levels are obtained by doses of 200–300 mg every 6–8 hours. It is mostly metabolized by the liver and its metabolism and excretion are not significantly affected by renal failure. Mexiletine has very few deleterious drug interactions; more importantly, it does not affect digoxin blood levels. Its efficacy in controlling ventricular arrhythmias has been widely studied. The reported success rate varies from 84% to 52%. In our study of patients with symptomatic and refractory ventricular arrhythmias, the success rate with mexiletine was 55% initially and 33% at one year. Mexiletine appears to be most useful in combination with other anti arrhythmic agents such as propranolol, quinidine, procainamide, or amiodarone. Mexiletine has very few cardiac side effects. It was found not to have significant negative inotropic effects even in patients with congestive heart failure. Its major side effects, however, include gastric intolerance. Other less common side effects include central nervous system manifestations. Like all other antiarrhythmics, it can potentially aggravate ventricular arrhythmias in about 10% of patients but in most cases the proarrhythmic effect is not Clin cally significant.

Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin

Nadolol, a long-acting beta-adrenergic-blocking agent, was evaluated in 20 patients with chronic atrial fibrillation by means of a randomized, double-blind, crossover study. Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation (3 minutes, 1.75 mph, 10% grade). With placebo the group averaged a heart rate of 92 ± 19 bpm, determined by 24 hours of ambulatory ECG recordings; this rate was significantly reduced to 73 ± 16 bpm ( p < 0.001) with nadolol (mean dosage, 87 ± 43 mg/day). During standardized exercise testing, heart rates increased to 153 ± 26 bpm with placebo and to 111 ± 24 bpm with nadolol ( p < 0.001), representing 65% and 52% increments, respectively. Digoxin blood levels averaged 0.8 ± 0.5 ng/ml with placebo and were similar with nadolol (0.9 ± 0.4; p = NS). Total exercise time on a modified Bruce treadmill protocol was 466 ± 143 seconds with placebo and was significantly decreased by nadolol (380 ± 143; p < 0.01). During initial dose titration with nadolol, one patient was dropped from study for intolerable fatigue and one for worsened claudication. No patients were dropped from the double-blind treatment periods, although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue. We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment.

Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis

The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind, randomized, crossover study. The heart rate in patients who received verapamil compared with placebo group was lower at rest (mean 69 ± 13 versus 87 ± 20 beats/min, p <0.01), as was the degree of tachycardia at the end of 3 minutes of a standardized exercise test (104 ± 14 versus 136 ± 23 beats/min, p <0.01). Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients, 320 mg/day in 6 patients, and 480 mg/day in 3 patients. Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study. Two patients were discontinued from the study because of adverse reactions. No clinically significant changes during verapamil therapy were observed on the electrocardiogram, chest roentgenogram, echocardiogram or in the laboratory evaluation. Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo (1.23 ± 0.59 versus 0.85 ± 0.46 ng/ml, p <0.01), but no patient had signs or symptoms of digitalis toxicity. Thus, oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia.

Hemodynamic effects of encainide in patients with ventricular arrhythmia and poor ventricular function

Gated cardiac scanning was used to evaluate the hemodynamic effects of encainide in 19 patients (1 woman) with complex ventricular arrhythmia and depressed left ventricular (LV) function (ejection fraction <45 %). Patients were 36 to 80 years old (average 61). All were candidates for long-term encainide therapy after having failed with currently available antiarrhythmics. Sixty-three percent had congestive heart failure before they received encainide. All were evaluated in the hospital before encainide therapy by a gated cardiac scan performed at least 3 days after discontinuing all antiarrhythmic drugs. Patients received oral encainide in doses of 75 to 200 mg. Gated cardiac scans were repeated 1 to 2 weeks later when an 80% reduction in frequency of premature ventricular complexes was observed on a 24-hour Holter recording. No patient had worsening of congestive heart failure during encainide therapy. Encainide did not significantly affect ejection fraction, which averaged 22 ± 10% before and 25 ± 14% (SD) after encainide (difference not significant [NS]). Other hemodynamic variables, including heart rate, blood pressure, stroke volume and end-diastolic volume, remained unchanged during encainide therapy. Digoxin blood levels in 10 patients averaged 1.04 ±0.43 before and 1.22 ± 0.47 mg/ml (NS) during encainide therapy. Thus, encainide given orally in clinically effective doses does not appear to have significant hemodynamic effects in patients with ventricular arrhythmia and depressed LV function.

Evaluation of Several Surface-Active Agents on Digoxin Rectal Absorption

Rectal suppositories of digoxin were made with cacao butter containing 5% of polysorbate 60, SFAE-11, SFAE-15, SML, GMS, and PGMS. Physical properties, melting point, dissolution time, and hardness of these suppositories were measured. Blood levels of digoxin in rabbits after rectal administration (0.3mg/kg) were determined by a radioimmunoassay method. Bioavailability was estimated by measuring the relative area under the concentration-time curve for digoxin suppositories. Plasma digoxin concentrations of suppositories containing SML, GMS, and PGMS were poor. The relative AUC for digoxin suppositories containing SFAE-15, SFAE-11, SML, GMS, and PGMS were 0.90, 1.02, 0.23, 0.27, and 0.23 respectively when a suppository containing polysorbate 60 was used as the standard. The ratio between 1.5-hour value and 0.5-hour value of plasma digoxin concentration after rectal administration for suppositories containing SFAE-15, and SFAE-11 were 0.56 and 0.65. The highest plasma digoxin concentration was obtained with suppository containing SFAE-15 and plasma digoxin level was kept for a long time with suppository containing SFAE-11.

DO WE NEED A THREE-COMPARTMENT MODEL FOR THE PREDICTION OF DIGOXIN BLOOD LEVELS ON MULTIPLE DOSING?

Journal of Clinical Pharmacy and TherapeuticsVolume 5, Issue 1 p. 31-34 DO WE NEED A THREE-COMPARTMENT MODEL FOR THE PREDICTION OF DIGOXIN BLOOD LEVELS ON MULTIPLE DOSING? L. Balant, Corresponding Author L. Balant Policlinique de Médecine, University of Geneva, Switzerland2 Policlinique Universitaire de Médecine, CH-1211 Genève 4, Switzerland.Search for more papers by this authorC. A. Hunt, C. A. Hunt *School of Pharmacy, University of California, San Francisco, U.S.A.Search for more papers by this author L. Balant, Corresponding Author L. Balant Policlinique de Médecine, University of Geneva, Switzerland2 Policlinique Universitaire de Médecine, CH-1211 Genève 4, Switzerland.Search for more papers by this authorC. A. Hunt, C. A. Hunt *School of Pharmacy, University of California, San Francisco, U.S.A.Search for more papers by this author First published: February 1980 https://doi.org/10.1111/j.1365-2710.1980.tb00946.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume5, Issue1February 1980Pages 31-34 RelatedInformation

Inefficacy of digitalis in the control of heart rate in patients with chronic atrial fibrillation: Beneficial effect of an added beta adrenergic blocking agent

The role of digoxin and the new beta adrenergic blocking agent, timolol, in controlling heart rate at rest and during exercise was investigated in 28 patients with chronic atrial fibrillation. Digoxin failed to prevent excessively rapid heart rates during mild to moderate exercise. Increasing digoxin blood levels from a mean of 0.6 to 1.8 ng/ml had no effect on heart rate either at rest or during exercise. The addition of timolol, 20 to 30 mg/day, resulted in a satisfactory and significant attenuation of the rapid heart rates both at rest and during exercise. Heart rates at rest were 91 and 98 beats/min in the patients with low and high digoxin dosage and rose to 135 and 139 beats/min, respectively, during exercise. Timolol reduced the heart rate to 67 at rest and to 92 beats/min during exercise. The effect of beta adrenergic blockade at rest was less pronounced in patients whose initial heart rates were below 90 beats/min. Digoxin alone may not suffice to control excessive heart rate in patients with chronic atrial fibrillation. The additional beta adrenergic blockade actually normalizes the heart rate response in these patients.

Interpretation of Digoxin Blood Levels by Programmable Calculator

The usefulness of a computer algorithm, for a hand-held calculator, in the calculation of steady-state blood levels of digoxin was studied. The calculator was programmed using the Wagner-Northam steady-state equation. The program was tested on data obtained from the charts of 14 patients recieving digoxin. Blood levels of digoxin were determined by radioimmunoassay. In nine patients, the calculated values correlated well with measured values. In five patients, calculated values did not correlate with measured values; half-life was underestimated in two patients, a charting error was made with one patient and digoxin disappearance was suggested to be unusual in two patients. This study suggests that a measure of scientific precision in planning and monitoring of drug therapy regimens is possible using a programmable calculator.

Investigation of cardiac glycoside levels in human post mortem blood and tissues determined by a special radioimmunoassay procedure.

Even after the introduction of radioimmunological methods the question of a cardiac glycoside causing or contributing to the death of a patient can not be answered satisfactorily. By means of a special radioimmunoassay procedure for digoxin as well as for the structurally related methyl- and acetylderivatives we measured the concentrations in human blood and post mortem tissues. We investigated the glycoside contents in the blood of intravenously digitalised (Novodigal) al) patients before and after death. At autopsy blood specimens were taken from the heart and the femoral vein. We found an increase of the glycoside level up to a highly toxic range (7--15 ng/ml) especially in the heart blood. Thus post mortem blood levels of digoxin and its derivatives are not suitable for a final decision in alleged cases of fatal poisonings. Measuring various concentrations in tussues and body fluids of the above cardiac glycosides mentioned revealed the kidney concentration to be of high value in confirming a digitalis poisoning. This organ and the heart show the highest tissue concentrations. Interpretations of fatal digitalis poisonings should be based on the additional knowlege of these concentrations. Individual cardiac glycosides may be analyzed by a combination of thin layer chromatography and radioimmunoassay.

Infant versus adult plasma digoxin levels.

Summary: Plasma digoxin levels were measured in 22 adults and in 18 infants under one year. Of the adults, 12 had no evidence of toxicity and 10 had clinical and ECG evidence of digitalis intoxication. Mean value of plasma digoxin in the non-toxic adults was 1.41 (SD ±0.49) ng/ml. and was significantly higher in the toxic group — mean 3.81 ± 1.45 ng/ml. (p < 0.001). The mean value in infants, none of whom had clinical or ECG evidence of toxicity, was 3.45 < 2.09 ng/ml. – significantly higher than non-toxic adults (p < 0.005). In the two adult groups, the higher levels in toxic patients appeared to be related to impaired renal function and not to dosage. Although there was no relationship within the infants between dose and plasma digoxin level, they did as a group have a significantly higher mean plasma level and a significantly higher mean dose of digoxin relative to body weight than did the non-toxic adult group. Infants were noted to have higher serum potassium levels. Currently accepted adult ranges for differentiating therapeutic from toxic blood levels of digoxin are not applicable to infants.