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PubMed1992

Determination of salivary digoxin with a dry strip immunometric assay.

Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1-2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p less than 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight nondigitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring.

Adult↗
PubMed2004

Ritonavir decreases the nonrenal clearance of digoxin in healthy volunteers with known MDR1 genotypes.

Our objective was to examine the influence of ritonavir on P-glycoprotein (P-gp) activity in humans by characterizing the effect of ritonavir on the pharmacokinetics of the P-gp substrate digoxin in individuals with known MDR1 genotypes. Healthy volunteers received a single dose of digoxin 0.4 mg orally before and after 14 days of ritonavir 200 mg twice daily. After each digoxin dose blood and urine were collected over 72 hours and analyzed for digoxin. Digoxin pharmacokinetic parameter values were determined using noncompartmental methods. MDR1 genotypes at positions 3435 and 2677 in exons 26 and 21, respectively, were determined using PCR-RFLP analysis. Ritonavir increased the digoxin AUC(0-72) from 26.20 +/- 8.67 to 31.96 +/- 11.24 ng x h/mL (P = 0.03) and the AUC(0-8) from 6.25 +/- 1.8 to 8.04 +/- 2.22 ng x h/mL (P = 0.02) in 12 subjects. Digoxin oral clearance decreased from 149 +/- 101 mL/h x kg to 105 +/- 57 mL/h x kg (P = 0.04). Other digoxin pharmacokinetic parameter values, including renal clearance, were unaffected by ritonavir. Overall, 75% (9/12) of subjects had higher concentrations of digoxin after ritonavir administration. The majority of subjects were heterozygous at position 3435 (C/T) (6 subjects) and position 2677 (G/T,A) (7 subjects); although data are limited, the effect of ritonavir on digoxin pharmacokinetics appears to occur across all tested MDR1 genotypes. Concomitant low-dose ritonavir reduced the nonrenal clearance of digoxin, thereby increasing its systemic availability. The most likely mechanism for this interaction is ritonavir-associated inhibition of P-gp. Thus, ritonavir can alter the pharmacokinetics of coadministered medications that are P-gp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1-adrenoceptor agonist, and digoxin in healthy subjects.

1. Cicloprolol is a partial beta 1-adrenoceptor agonist considered for the treatment of patients with coronary artery disease and impaired left ventricular function. In such patients, digoxin remains in widespread use. 2. We assessed the pharmacokinetic and pharmacodynamic interaction between oral cicloprolol 50 mg day-1 and oral digoxin 0.25 mg day-1 in 10 healthy male volunteers, using a double-blind, randomised protocol, during three 8 day periods. Digoxin was given alone during the first period to reach steady state; then digoxin was given with cicloprolol or placebo during the second and third periods, according to a cross-over design. 3. No significant adverse effects were observed. 4. The pharmacokinetics of digoxin were not different significantly at the end of the placebo-digoxin and cicloprolol-digoxin periods. 5. A significant increase in minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter recordings, was observed at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 57.1 +/- 3.2 beats min-1 vs 52.2 +/- 3.1 beats min-1, P less than 0.01; and 65.6 +/- 3.8 beats min-1 vs 59.9 +/- 3.9 beats min-1, P less than 0.01, respectively). 6. A significant increase in left ventricular ejection fraction and shortening fraction, assessed by echocardiography, was noted at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 66.4 +/- 1.4% vs 61.3 +/- 1.2%, P less than 0.05; and 37.0 +/- 1.1% vs 33.3 +/- 0.9%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1996

Itraconazole increases serum digoxin concentration.

Itraconazole can interact with several drugs by inhibiting their metabolism. Many drugs known to increase serum digoxin concentration are inhibitors of CYP enzymes (e.g. verapamil, diltiazem, amiodarone, cyclosporine). Case reports suggest that itraconazole, added to digoxin therapy, may induce digoxin intoxications; hence we wanted to study their possible interaction. In this two-phase study ten healthy young volunteers ingested 0.25 mg of digoxin daily for 20 days. Concomitantly, they received either 200 mg itraconazole or placebo orally once daily for 10 days in a double-blind, randomized, cross-over study design. Serum concentrations of digoxin and itraconazole were measured (12 hr after administration) on days 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 20. Digoxin concentrations were measured by fluorescence polarization immunoassay and confirmed (days 10 and 20) by affinity column-mediated immunoassay. Itraconazole increased serum digoxin concentration in each of the subjects. On the 10th day of the placebo phase serum digoxin concentration was 1.0 +/- 0.1 nmol/l, and on the 10th day of the itraconazole phase 1.8 +/- 0.1 nmol/l (P < 0.001). Care should be taken if itraconazole is prescribed to patients using digoxin. The mechanism of the itraconazole-digoxin interaction is unclear but may be related to CYP3A4-mediated changes in the pharmacokinetics of digoxin.

Adult↗
PubMed1985

Influence of hypoxemia and respiratory acidosis on the plasma kinetics and tissue distribution of digoxin in the conscious dog.

The aim of the present study was to investigate the influence of hypoxemia combined with respiratory acidosis on the kinetics of digoxin in conscious dogs. One group of three beagles was exposed to air and 7 days later to 10% O2, 10% CO2, and 80% N2. In a second group of three dogs, the order of exposure to the two atmospheric conditions was reversed. The dogs received 25 micrograms/kg digoxin and blood and urine samples were collected over the next 29 h. At the conclusion of the second treatment, the dogs were sacrificed to determine digoxin concentrations in the left ventricle, liver, renal cortex, and skeletal muscle. Digoxin total body clearance increased from 6.2 +/- 0.9 in control to 9.0 +/- 1.0 mL X min-1 X kg-1 in hypoxemic and hypercapnic dogs (p less than 0.05). The digoxin apparent volume of distribution at steady state (Vss) was increased in the dogs with hypoxemia and hypercapnia (11.63 +/- 1.11 vs. 8.62 +/- 0.41 L/kg in the controls, p less than 0.05). As a consequence the digoxin plasma half-life remained unchanged (18.6 +/- 1.5 h in hypoxemic and hypercapnic dogs versus 20.1 +/- 2.8 h in the controls). In dogs with hypoxemia and hypercapnia, the ratio of tissue to plasma digoxin concentrations tended to increase in the liver, in the renal cortex, and in the left ventricle and remained unchanged in the left hind leg muscle. In vitro studies showed that the digoxin total binding to erythrocyte membranes was slightly increased in the dogs with hypoxemia and hypercapnia, resulting from an increase in the apparent intrinsic association constant for digoxin (p less than 0.003). It is concluded that hypoxemia combined with respiratory acidosis changes digoxin disposition in the conscious dog and is the cause of a digoxin redistribution into the tissues.

Acidosis, Respiratory↗
PubMed1975

Augmentation of myocardial digoxin concentration in hemorrhagic shock.

The effect of the shock state on myocardial digoxin uptake and plasma digoxin levels was examined in unanesthetized dogs following hemorrhage. Five minutes after intravenous administration of tritiated digoxin the myocardial digoxin content in animals with shock was greater than in normal animals in both left ventricle (LV) (165 plus or minus 15 (SD) ng/g vs 130 plus or minus 26 ng/g, P smaller than 0.02 and right ventricle (RV) (142 plus or minus 13 ng/g vs 111 plus or minus 22 ng/g. P smaller than 0.02) as was the plasma digoxin concentration (61.6 plus or minus 11.8 ng/ml vs 44.3 plus or minus 4.6 ng/ml, P smaller than 0.02). After one hour, in another group of dogs, the difference in myocardial concentration of digoxin between test and normal groups was even greater (LV: 213 plus or minus 26 ng/g vs 133 plus or minus 13 ng/g, P smaller than 0.001; RV: 171 plus or minus 9 ng/g vs 111 plus or minus 8 ng/g. P smaller than 0.001) despite lower plasma digoxin concentration in the test group (12.9 plus or minus 2.9 ng/ml vs 17.3 plus or minus 2.5 ng/ml, P smaller than 0.05). Diminished peripheral blood flow, peripheral digoxin delivery and uptake were probably responsible for the early difference in plasma digoxin levels. Resultant greater plasma concentrations of digoxin presented to the myocardium in the early phase, coupled with relative preservation of myocardial blood flow, may explain the greater myocardial uptake in animals with shock although myocardial mechanical factors may also be implicated. Augmented uptake of digoxin by the myocardium in canine hemorrhagic shock may be relevant to the altered susceptibility to glycoside action in clinical shock syndromes.

Animals↗
PubMed1982

The influence of verapamil on serum digoxin concentration.

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.

Adult↗
PubMed1976

Renal tubular transport of 3H-digoxin in saline diuresis in rats.

We evaluated urinary excretion and tubular transport of 3H-digoxin by three different methods in anesthetized rats made diuretic by infusion of 2.5% saline. In one group small volumes of 3H-digoxin and 14C-inulin were injected simultaneously into surface proximal convolutions, and urine was collected serially from both ureters. Digoxin recovery was lower after early (62.1 +/- 5.3%) than after late (86.9 +/- 7.7%) proximal administration but inulin recovery was complete (99.6 +/- 2.7%) after all injections. Most of the digoxin was excreted simultaneously with inulin. Delayed recovery was low. In another group of rats digoxin and inulin were applied directly to the capsule of the left kidney. Two-thirds of the recovered digoxin appeared from the left ureter and one-third from the right. The difference (41.9 +/- 7.4%) is an estimate of transtubular digoxin influx. Digoxin excretion preceded inulin only on the left. Digoxin to inulin concentration ratios were 6 times higher from the left than the right, whereas inulin recoveries from the two sides were similar. In a third group of rats tubular fluid was collected from surface convolutions of proximal and distal tubule. In the accessible segment of the proximal tubule 35.9% of the filtered digoxin was reabsorbed. In the more distal nephron, drug was added into the lumen; this resulted in a net urinary excretion of 80.2 +/- 18.2%. These findings are compatible with free filtration of digoxin at the glomerulus followed by passive proximal tubular reabsorption and an influx against a concentration gradient in the distal nephron.

Animals↗
PubMed1985

The influence of hypoxemia on tritiated digoxin plasma kinetics and tissue distribution in the conscious dog.

The goals of this study were to document the effect of hypoxemia on the distribution of digoxin in conscious dogs. For this purpose, 6 beagles were exposed to air and 6 others to an atmosphere containing 10% O2, to generate a PaO2 equal to 46.3 +/- 0.3 mmHg (mean +/- SEM). The animals received 25 micrograms/kg of digoxin containing 2.17 micrograms/kg of 3H-digoxin, and then blood and urine samples were collected over the next 48 h, at which time they were killed to determine digoxin concentrations in several tissues. Five additional beagles were used to assess the influence of hypoxemia on the blood perfusion to these tissues using radioactive microspheres. The results, expressed as digoxin equivalents, indicated that hypoxemia increased the digoxin apparent volume of distribution (2.85 +/- 0.10 versus 2.01 +/- 0.11 L/kg; p less than 0.001) and the time required to achieve this distribution (9.7 +/- 1.4 versus 2.6 +/- 0.3 h; p less than 0.01). As digoxin clearance was not influenced by hypoxemia, the half-life was increased from 25.2 +/- 1.5 to 33.4 +/- 1.3 h (p less than 0.01). With hypoxemia, digoxin concentrations increased significantly in the brain and diaphragmatic muscle, but only marginally in other organs, including the heart, the latter despite a significant increase in blood flow. It is concluded that hypoxia does change digoxin disposition but does not increase digoxin heart concentrations. Therefore, factors other than changes in digoxin plasma kinetics and heart distribution may be responsible for the decrease in digitalis tolerance during hypoxemia.

Animals↗
PubMed1985

Digoxin and cimetidine: investigation of the potential for a drug interaction.

The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

Adult↗
PubMed1990

Fetal uptake of intraamniotic digoxin in sheep.

To explore the possibility that intraamniotic administration of digoxin is an effective treatment regimen for fetal tachyarrhythmia, we injected digoxin into the amniotic fluid cavity of pregnant sheep and examined the time course of digoxin distribution to the fetal and maternal plasma compartments. Animals were studied in two groups according to digoxin dosage: 0.7-1.8 nmol/kg fetal body wt in the high-dose group (n = 6) and 0.1-0.6 nmol/kg fetal body wt in the low-dose group (n = 14). Within 1 h, plasma digoxin concentrations in the high-dose and low-dose groups were 18.2 +/- 15.0 nmol/L and 2.7 +/- 0.8 nmol/L, respectively (values are expressed as mean +/- SD). At 6 h digoxin concentrations were 13.8 +/- 7.0 and 3.1 +/- 0.9 nmol/L, and at 24 h they were 2.3 nmol/L (n = 1) and 1.8 +/- 1.2 nmol/L, respectively. Peak maternal digoxin levels were about one-tenth fetal values in the high-dose group and undetectable in the low-dose group. Fetal digoxin concentrations were significantly greater in the descending aorta than in the umbilical vein (p less than 0.02). Fetal arterial blood pressure and heart rate were not significantly different from control at any time after digoxin administration. These results demonstrate that digoxin is rapidly taken up into the fetal circulation from the maternal amniotic cavity. The exact mechanism whereby this occurs is unknown, but transplacental transfer from the maternal circulation is not involved. Our findings suggest that intraamniotic administration of digoxin may be an alternative treatment for fetal tachyarrhythmias when direct administration of antiarrhythmic agents is ineffective or produces maternal toxicity.

Amnion↗
PubMed2005

Properties of novel anti-digoxin antisera in radioimmunoassay using homologous and site heterologous tritium-labeled antigens involving a [3H]-leucine moiety.

The specificities of antisera against digoxin C-3' or C-3'' hemisuccinate-bovine serum albumin (BSA) conjugate were assessed by cross-reactivity studies with digoxin metabolites by radioimmunoassay (RIA) using the homologous and the site heterologous tritium-labeled antigens. One of the tracers used was digoxin 3'-hemisuccinyl-[3H]-leucine; the other was digoxin 3''-hemisuccinyl-[3H]-leucine, which had been prepared from digoxin 3''-hemisuccinate. When the tracer with [3H]-leucine at the C-3' position was used, antisera (I-1, I-3) elicited by digoxin 3'-hemisuccinate-BSA conjugate showed the following cross-reactivity: digoxigenin bisdigitoxoside (0.34%, 76%), digoxigenin monodigitoxoside (0.11%, 65%), digoxigenin (0.02%, 26%) and dihydrodigoxin (9.4%, 1.2%). However, when using the homologous antigen, antiserum (I-1) was highly specific against the digitoxose chain. When the site heterologous antigen, digoxin 3''-hemisuccinyl-[3H]-leucine was combined, this antiserum showed high cross-reactivity to digoxin degradation products. This digoxin RIA using antiserum (I-1) with the homologous antigen measures unmetabolized digoxin. On the other hand, the RIA system using antiserum (I-3) with the homologous antigen had cross-reactivity with the metabolites in accordance with their relative cardio-activities, so this system would be useful in therapeutic drug monitoring of digoxin.

Animals↗
PubMed2000

Effect of aging on the incidence of digoxin toxicity.

OBJECTIVE: To evaluate the relationship of the therapeutic serum digoxin concentration (SDC) range (0.5-2 ng/mL, as recommended in previous clinical studies) with the incidence of digoxin toxicity during digoxin maintenance therapy. METHODS: Subjects included all inpatients (n = 462) and outpatients (n = 437) receiving digoxin oral maintenance therapy for heart failure and/or atrial fibrillation with tachycardia at Kosei Hospital, Anjo, Japan. SDC and blood chemistry analysis were determined, and a 24-hour Holter electrocardiographic recording was performed when the SDC was at the presumed steady-state concentration. RESULTS: Analysis of clinical data showed that there was an overlapping (toxic and nontoxic) range of SDCs in which the incidence of digoxin toxicity was patient-dependent (1.4-2.9 ng/mL). No patient exhibited signs or symptoms of digoxin toxicity when the SDC was <1.4 ng/mL; all patients had evidence of toxicity when the SDC was >3 ng/mL. Additionally, it was shown that the concentration range of this overlapping range tended to broaden and shift to lower concentrations with increasing age. Patients with signs of toxicity when their SDCs were in the overlapping range had normal serum creatinine, blood urea nitrogen, digoxin clearance, creatinine clearance, and potassium concentrations, except for a significantly higher mean age than patients without toxicity. The incidence of digoxin toxicity was dependent on increasing age in patients whose SDCs were within the recommended therapeutic range. Moreover, clinical evidence of digoxin toxicity in patients >71 years old was 26.5%, despite their SDCs falling between 1.4 and 2 ng/mL. CONCLUSIONS: Increased age is most likely associated with enhanced susceptibility to digoxin toxicity, possibly due to unknown pharmacodynamic changes. This raises the possibility that patients >71 years show clinical evidence of digoxin toxicity despite having SDCs within the recommended therapeutic range.

Age Factors↗
PubMed1991

Determination of digoxin in the blood of pregnant women, fetuses and neonates before and during anti-arrhythmic therapy, using four immunochemical methods.

Four immunochemical methods for digoxin assay were used to analyse control samples, 33 amniotic fluid samples, 57 samples from digitalis-treated, non-pregnant women, 90 pregnancy serum samples, and 72 samples of fetal or neonatal serum with or without digoxin therapy. One hundred and five samples were also submitted to ultrafiltration before analysis. Three methods (RIA, TDX, AMERLITE) showed practically the same precision, while the precision of the DELFIA was markedly inferior. In the analysis of serum samples from digoxin-treated, non-pregnant women, RIA and TDX gave practically the same values, whereas AMERLITE and DELFIA gave significantly higher values. Pregnancy serum and fetal serum contain "digoxin-like immunoreactive factors", and the qualitative and quantitative effects of these interfering factors are different for each of the four methods. The greatest sensitivity to "digoxin-like immunoreactive factors" is shown by TDX and DELFIA, while the lowest interference by "digoxin-like immunoreactive factors" is found in the analysis of ultrafiltered samples, using the TDX method. The composition of the "digoxin-like immunoreactive factors" in pregnancy serum and in fetal serum is altered by digoxin therapy, and these changes have different effects on the various analytical methods. The concentration of "digoxin-like immunoreactive factors" in the serum of fetuses receiving digoxin is markedly lower than that of healthy fetuses. For the reliable monitoring of digoxin therapy in the maternal and fetal circulation, the blood samples must be submitted to ultrafiltration before analysis.

Amniotic Fluid↗
PubMedDate not supplied

Digoxin toxicity in the aged. Characterising and avoiding the problem.

Digoxin is one of the most frequently prescribed drugs, particularly in the elderly population where there is an increased prevalence of atrial fibrillation and cardiac failure. The drug has a narrow therapeutic range and has gained a reputation for producing adverse effects in older patients. The more frail elderly patients with coexistent disease, often taking other treatments, are more at risk from digoxin toxicity due to inappropriate dosing, noncompliance, or increased sensitivity to digoxin resulting from pharmacokinetic or pharmacodynamic interactions. Application of basic pharmacological principles may be helpful in anticipating these problems. Elderly patients more commonly receive digoxin than younger patients, which in part accounts for the higher rates of toxicity in this group. Numerous components contribute to the development of toxicity, and diagnosis of toxicity is difficult in this age group. The measurement of serum concentrations can contribute to the clinical diagnosis. A major problem is the accurate diagnosis of digoxin toxicity which may have numerous nonspecific clinical manifestations, many of which are related to coexisting disease in elderly patients. This diagnostic imprecision is well recognised but has been helped by the introduction of serum digoxin measurement. However, reliance on serum concentrations should not replace clinical judgement, since these do not always correlate with toxicity. The apparently decreasing incidence of toxicity over recent years probably reflects several factors: the improvement in digoxin formulations, awareness of digoxin pharmacology, utilisation of serum concentrations, and the realisation that digoxin withdrawal is a viable proposition in elderly patients. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin overdose, especially in the elderly population.

Aged↗
PubMed1997

When, and when not, to use digoxin in the elderly.

Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Generally, first-line therapy for the management of heart failure due to systolic dysfunction should include an ACE inhibitor and a diuretic. In patients who remain symptomatic despite the use of these drugs, the addition of digoxin should be considered. Because digoxin has been shown to reduce the number of hospital admissions attributable to worsening heart failure, more liberal use of digoxin in the management of heart failure may be justified. Digoxin may be adequate as monotherapy for ventricular rate control in patients with chronic AF, particularly in sedentary and elderly patients. A beta-blocker or calcium antagonist (either alone or in combination with digoxin) is indicated when digoxin is ineffective for ventricular rate control. Digoxin is ineffective in restoring sinus rhythm, preventing paroxysms or controlling rate in paroxysmal AF. The elderly are at an increased risk of digoxin toxicity. Low dosages of digoxin appear to be effective in the treatment of heart failure due to systolic dysfunction and may reduce the incidence of digitalis toxicity in these patients. In elderly patients with AF and inadequate rate control who are receiving digitalis monotherapy, adding another atrioventricular nodal blocking drug may be more appropriate than increasing the digoxin dose, in order to avoid toxic digoxin levels.

Aged↗
PubMed1976

Bioavailability of drugs: the digoxin dilemma.

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.

Biological Availability↗
PubMed2004

Cystatin C vs creatinine as markers of renal function in patients on digoxin treatment.

BACKGROUND: The kidney function is a major determinant of the serum concentration of digoxin as this drug is mainly eliminated unchanged through the kidneys. Since digoxin is widely prescribed among the elderly, and the glomerular filtration rate (GFR) declines with age, it is important that the clinician takes the patient's GFR into account when prescribing digoxin. Serum cystatin C has been suggested to be superior to creatinine for estimation of GFR, which may have relevance for the optimization of treatment with digoxin. METHODS: To evaluate which of the two GFR markers serum creatinine and serum cystatin C that best correlates with serum digoxin, we compared the serum levels of digoxin with the serum levels of creatinine and cystatin C in 149 patients on therapeutic drug monitoring of digoxin at our hospital. RESULTS: Overall, there was a stronger correlation between serum digoxin concentrations and cystatin C (p=0.00001) as compared to creatinine (p= 0.00003). Interestingly, of the patients with a serum digoxin concentration > or = 1.5 nmol/L, 29% had a serum creatinine level within normal limits, as compared to 20% with normal cystatin C levels. CONCLUSIONS: In this study, serum cystatin C correlated better to serum digoxin than did serum creatinine. With improved GFR monitoring, digoxin concentrations should be better controlled.

Aged↗