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PubMed1989

Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects.

Previous reports have suggested an interaction between propafenone and digoxin. We investigated the pharmacokinetics of IV digoxin when given alone (Phase I), after pretreatment with propafenone 150 mg every 8 hours for seven days (Phase II), and after propafenone 300 mg every 8 hours for 7 days (Phase III). The total body clearance of digoxin during Phase I was 2.45 ml/min/kg and was 2.17 ml/min/kg during Phase II (NS) and decreased to 1.92 ml/min/kg during Phase III (P less than 0.05). The renal clearance and half-life of digoxin were not significantly altered by propafenone. There was a trend towards a decrease in the volume of distribution of digoxin from 9.43 L/kg in Phase I, to 9.33 L/kg in Phase II, and 8.02 L/kg in Phase III. Similarly there was a trend towards a decreased nonrenal clearance of digoxin from 1.21 ml/min/kg during Phase I to 1.01 ml/min/kg during Phase II and to 0.75 ml/min/kg during Phase III. The changes in volume of distribution and nonrenal clearance parallel each other resulting in no change in the elimination half-life of digoxin. It is postulated that the mechanism of this interaction is due to decreases in the volume of distribution and nonrenal elimination of digoxin by propafenone. The degree of this interaction was related to the dose of propafenone. The magnitude of this interaction may be greater in patients and, thus, may require a reduction in the digoxin dose.

Adult↗
PubMed1980

Digoxin degradation in acidic dissolution medium.

The release of digoxin and its simultaneous conversion to digoxigenin bisdigitoxoside, digoxigenin monodigitoxoside, and digoxigenin in a USP dissolution test medium were followed by high-pressure liquid chromatography. Two products, Tablets A and B, were manufactured by solvent deposition and simple blending methods, respectively. Tablet A released digoxin faster than Tablet B in distilled water and in artificial intestinal juice, and no decomposition was observed. In the USP dissolution test medium, the rate of hydrolysis to digoxigenin bisdigitoxoside was almost equal to that of hydrolysis to digoxigenin monodigitoxoside, and a comparatively large formation rate of digoxigenin was observed. Concentrations of digoxin and its decomposition products were described by differential equations that included dissolution rates of digoxin (rapidly dissolving digoxin and digoxin crystals) and an apparent hydrolysis rate. In the earlier stage of dissolution, hydrolysis was rate determining; in the later stage, dissolution became the rate-determining step for overall digoxin degradation. To suppress digoxin hydrolysis in the USP dissolution test medium, a developmental formulation study was performed. The incorporation of magnesium oxide and magnesium hydroxide-aluminum hydroxide in the tablet formulations inhibited digoxin hydrolysis by 15.3 and 14.5%, respectively, after dissolution for 30 min without serious delay of drug release.

Acids↗
PubMed1982

Investigation of digoxin, quinidine, and disopyramide interactions in rats utilizing parotid saliva, blood, and other tissues.

Blood, parotid saliva, heart, liver, and kidney concentrations of digoxin and quinidine were determined in rats chronically treated with digoxin and in nontreated (control) rats after the administration of quinidine (20 mg/kg ip) and disopyramide (10 mg/kg ip). The results indicated that digoxin concentrations increased significantly and proportionally in parotid saliva and plasma after quinidine, but did not increase after disopyramide. With the exception of the liver, which showed an increase in digoxin concentrations, tissue concentrations of digoxin did not differ from control animals. In rats pretreated chronically with digoxin, quinidine concentrations in plasma, parotid saliva, or heart tissue did not differ significantly from control animals, but were significantly lower than controls in liver and kidney tissues. The results presented here lend additional support to the hypothesis that the increase in digoxin plasma concentration following quinidine administration is primarily due to interference with renal excretion and displacement of digoxin by quinidine binding sites. Furthermore, its was demonstrated that disopyramide has little or no effect on plasma digoxin levels in rats.

Animals↗
PubMed1988

Transport of digoxin into brain microvessels and choroid plexuses isolated from guinea pig.

To characterize the efflux system of digoxin, a cardiac glycoside, from the brain to the blood through the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, the accumulation of digoxin by the brain microvessel or the choroid plexus isolated from guinea pig brain was investigated. The accumulation of digoxin by the brain microvessel has a saturable component (Km = 0.163 microM, Vmax = 0.142 nmol/mL of tissue/min), with a nonsaturable component [Kd = 0.203 cell-to-medium (C:M) ratio/min] that was decreased by hypothermia (Q10 = 2.9), sulfhydryl reagent, and quinidine, but not by a metabolic inhibitor [2,4-dinitrophenol (DNP)]. It was concentration- and Na+-dependent. The accumulation of digoxin by the choroid plexus was also saturable (Km = 1.9 microM, Vmax = 3.8 nmol/mL of tissue/min), and was decreased by hypothermia (Q10 = 4.4), sulfhydryl reagents, ouabain, and quinidine, but not by metabolic inhibitors (DNP, KCN); it was also concentration- and Na+-dependent. The binding of digoxin to the homogenate of choroid plexus was one-tenth of digoxin accumulation by the intact choroid plexus, suggesting that digoxin is transported into the cells and bound to the cytosol fraction. The value of (Vmax/Km + Kd) multiplied by the total tissue weight of the microvessel per guinea pig is approximately 10-fold that of Vmax/Km multiplied by the tissue weight of the choroid plexus, although (Vmax/Km + Kd) per milliliter of the microvessel is half the Vmax/Km value of the choroid plexus. These findings suggest that digoxin can be excreted from both the brain and the cerebrospinal fluid to blood by a carrier-mediated diffusion system which is inhibited by quinidine, and that a main route of digoxin efflux from the brain to the blood is not through the blood-CSF barrier, but through the blood-brain barrier.

Animals↗
PubMed1996

Simultaneous isolation of endogenous digoxin-like immunoreactive factor, ouabain-like factor, and deglycosylated congeners from mammalian tissues.

DLIF (digoxin-like immunoreactive factor) and OLF (ouabain-like factor) are endogenous steroid-like ligands (approximately 781 and 595 Da, respectively) with molecular and structural properties similar to the plant-derived cardiac glycosides, digoxin and ouabain. We developed a purification method with a sufficiently wide range of extraction solubility to separate compounds with polarities spanning those of ouabain and digoxin. This technique provides a rapid, reliable, and efficient method for simultaneously isolating DLIF, OLF, and several naturally existing deglycosylated congeners, including three deglycosylated species of DLIF (DLIF-genin, DLIF-mono, and DLIF-bis) and one deglycosylated species of OLF (OLF-genin). Separation is achieved using acid extraction, C-18 reverse-phase HPLC chromatography, and signal detection using two antibodies, one specific for digoxin and one for ouabain. The average extraction efficiency is 400 pmol digoxin equivalent (range 300-500) and 42 pmol ouabain equivalent (range 37-50) per gram of adrenal cortex for DLIF and OLF, respectively. The relative molar immunoreactivity of DLIF is 10(3)-fold less than that of digoxin, whereas that of OLF is unity compared to ouabain, suggesting that OLF is structurally more similar to ouabain than DLIF is to digoxin. Of interest is the presence of a compound reacting with both digoxin and ouabain antibodies. This unique immunoreactive species is liekly to have structural similarity to both digoxin and ouabain and thus may represent a metabolic link between DLIF and OLF.

Adrenal Glands↗
PubMed1998

Digoxin effects in the guinea pig heart: interaction with rimalkalim.

The aim of this study was to examine the influence of pre-treatment with rimalkalim (formerly HOE 234), an activator of ATP-sensitive K+ channels (KATP), on the chronotropic, inotropic and electrophysiological effects of digoxin in the guinea pig heart. To study these effects we used spontaneously beating right atria and isolated papillary muscles from the guinea pig heart. The following parameters were measured: the heart rate (b.p.m.), force of contraction (Fc), rate of rise (+dF/dt) and rate of fall (-dF/dt) of force of contraction, time to peak contraction (ttp) and time to 10% of total amplitude of force (tt10), action potential (RP, APA, APD, Vmax) and effective refractory period (ERP). Apart from the positive inotropic effect, digoxin induced negative chronotropic action at the concentration of 30 microM. Digoxin also significantly decreased APD50 and APD90 duration and reduced APA and RP. Rimalkalim itself, has similar electrophysiological and chronotropic effects to digoxin, but opposite to digoxin, a negative inotropic action and hyperpolarisation of the isolated tissue. After pre-treatment with rimalkalim (1 microM), the significant potentiation of maximum positive inotropic effect (Emax) of digoxin has been observed, as well as a significant shortening of the duration of ttp, tt10 and ERP when compared with the values obtained with digoxin alone. Furthermore, a significant increase in Vmax occurred, compared to the value obtained with rimalkalim. Glibenclamide (1 microM), a selective inhibitor of ATP-sensitive K+ channels, added to rimalkalim, prevented the changes in digoxin action observed after pre-treatment with rimalkalim. The results demonstrate significant influence of pre-treatment with rimalkalim on digoxin-induced inotropic and electrophysiological effects in the guinea pig heart. An abolishing action of glibenclamide on this effect of rimalkalim suggests that an activation of ATP-sensitive K+ channels might cause these changes.

Animals↗
PubMed1983

Physical exercise and digoxin binding to skeletal muscle: relation to exercise intensity.

The effect of a 1 h bicycle exercise test on digoxin concentration in skeletal muscle (thigh) and serum was studied in 10 healthy men, who had ingested digoxin 0.5 mg daily for 2 weeks. During maintenance digoxin treatment each subject performed 2 exercise tests, at 70-90 W and 140-180 W both 24 h after the last dose, at a 2-7 day interval. During exercise at the lower work load the mean skeletal muscle digoxin concentration increased by 9% (n.s.) and the mean serum digoxin concentration decreased by 26% (p less than 0.001). The high work load induced a mean increase in skeletal muscle digoxin of 20% (p less than 0.05) and a mean decrease in serum digoxin of 40% (p less than 0.001). The results indicate that the increased uptake of digoxin into exercised skeletal muscle and the decrease in serum digoxin during exercise is related to the intensity of the exercise.

Adult↗
PubMed1983

Influence of verapamil on the inotropism and pharmacokinetics of digoxin.

Verapamil has been demonstrated to inhibit the elimination of digoxin and to increase its steady state plasma level by 60-80%. Animal studies suggest that verapamil abolishes the intropic action of other drugs such as ouabain and dopamine. The clinical consequences of this drug interaction were investigated by examining the inotropic activity of single doses of digoxin (assessed from systolic time intervals), with and without coadministration of verapamil. Verapamil decreased total-body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg (p less than 0.001) and increased the plasma half-life of the drug from 33.50 +/- 2.38 to 41.31 +/- 2.27 h (p less than 0.01). Verapamil had no influence on the base-line values of the systolic time intervals. Both in the absence and presence of verapamil, digoxin caused significant shortening of the total electromechanical systole and the left ventricular ejection time. However, compared to control conditions, the decay of these changes was slower in the presence of verapamil, in parallel with the prolongation of the plasma half-life of digoxin. A linear relationship was established between reductions in the systolic time intervals and the computer-derived concentration of digoxin in the deep compartment. These regression lines, which represent the concentration-effect relationships of the inotropism of digoxin, were not affected by verapamil. Thus, verapamil per se had no measurable effect either on base-line contractile function of the heart or on digoxin-induced inotropism. The elevated plasma digoxin concentration induced by verapamil appears cardioactive in terms of inotropism.

Adult↗
PubMed1985

On the interaction between phenytoin and digoxin.

An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC0-48 from 31.6 to 24.4 ng X ml-1 X h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml X min-1. Assuming no change in beta-acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml X min-1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.

Adult↗
PubMed1977

Plasma and urinary digoxin in thyroid dysfunction.

The response to a single oral dose of 0.5 mg digoxin has been studied in eight patients, of whom four were hyperthyroid and four were hypothyroid, both before and after treatment for their thyroid dysfunction. The post-dose plasma digoxin levels were significantly lower in the hyperthyroid patients when they were thyrotoxic than when they became euthyroid. In only one hypothyroid patient was the post-dose plasma digoxin level significantly higher before treatment than it was after and in the others the digoxin values reached were either the same as, or lower than, before treatment. There was a significant correlation between the creatinine clearance and the urinary concentrations of digoxin and these both altered with change in thyroid status. Total urinary digoxin excretion did not change. Pharmacokinetic analysis suggested that digoxin was distributed in a way compatible with a two-compartment model and that the volume of the central compartment was high in thyrotoxic patients and low in hypothyroid patients. In both cases it reverted to a median value after treatment. It is recommended that plasma digoxin levels should be monitored in all patients with thyroid dysfunction who require therapeutic digoxin.

Aged↗
PubMed1978

Steady state serum concentrations and renal clearance of digoxin in neonates, infants and children.

Steady state serum concentrations of digoxin were determined repeatedly in 34 infants with congenital heart disease. Simultaneous measurements of renal clearances of digoxin, creatinine and urea were obtained in 29 of the subjects. Serum digoxin concentrations were markedly higher in children under the age of 3 months than in those over this age, despite equal weight--adjusted 24 h doses. This finding was explained by a very rapid increase in renal digoxin clearance in the first 3 months--32 +/- 7 ml/min/1.73m2 at 1 week to 65.6 +/- 30 at 3 months. The subsequent increase in digoxin clearance was much slower, e. g. to 87.7 +/- 43 ml/min/1.73m2 at 12 months. Renal clearance of digoxin was equally well correlated with creatinine clearance (r = 0.87) as with urea clearance (r = 0.83), but it exceeded that of creatinine in all age groups. The findings indicate that both glomerular and tubular function is involved in the renal elimination of digoxin in young children, and that development of renal elimination of the drug parallels that of the maturation of renal function in the early months of life. The neonate and infant with congestive heart failure display impaired ability to eliminate digoxin. The impairment lessens rapidly with the development of renal function over the first 3 months of life. Diminished doses of digoxin should be advocated in this age group if therapeutic serum concentrations of the drug are to be maintained and toxicity avoided.

Aging↗
PubMed1975

[Simplified rapid determination of plasma digoxin. Methods and clinical evaluation].

The introduction of the Gamma Coat 125I-Digoxin Radioimmunoassay has simplified the digoxin determination to an extent that it may be used even in general hospitals with an intensive care unit. The total time for a stat determination has been reduced to 70 min. The coefficient of variation of the digoxin determination at low levels (less than 0.8 ng/ml) was less than 15% for simultaneous and repeated measurements even when using one of the inexpensive nuclear counting systems. At high levels (greater than 2.5 ng/ml) the coefficient of variation showed to be less than 6%. Hemolysis, low albumine concentration and other than digoxin-bound isotopes in the blood samples did not cause methologic problems. Provided that resorption and elimination kinetics of the different digoxin preparations were taken into account, digoxin levels of more than 2 ng/ml as measured by the Gamma Coat method in patients with normal renal function plasma were usually associated with clinical signs of overdosage; therapeutic concentrations were mostly higher than 1.2 ng/ml. The incidence of digitalis toxicity with high digoxin levels was lower in uremic than in normal patients. According to preliminary observations in dialysis patients this increase in tolerance to digitalis, may be a consequence of hyperkalemia and renal acidosis. Erroneously high digoxin concentrations were found in patients up to 2 hrs after injection of high doses of spironolactone (400-1000 mg) due to cross reaction. Therapeutic concentrations of digitoxin (10-25 ng/ml) caused only subtherapeutic digoxin concentrations of 0.4-0.9 ng/ml.

Anuria↗
PubMed1990

Investigation of possible pharmacokinetic and pharmacodynamic interactions between epanolol and digoxin.

The possibility of a pharmacokinetic and/or pharmacodynamic interaction between epanolol and digoxin has been investigated in 10 healthy male subjects taking digoxin 0.375 mg daily for 14 days. During that period epanolol 200 mg daily or matching placebo was also given, each for 7 days, according to a double-blind, randomized cross-over plan. The plasma digoxin concentration-time profiles after 7 days of concomitant placebo or epanolol were comparable. Trough and peak plasma digoxin levels were similar (placebo: 0.84 and 2.62 ng.ml-1; epanolol: 0.87 and 2.46 ng.ml-1). The renal clearances of digoxin and creatinine were lower during treatment with epanolol, but the differences were not significant (placebo 142.0 and 126.5 ml.min-1; epanolol 105.7 and 109.3 ml.min-1). STI indexes were lower during treatment with digoxin plus epanolol, than after digoxin alone. The difference was significant for QS2I (513 versus 503 ms), PEPI (119 versus 112 ms) and PEP/LVET (0.286 versus 0.304). The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between epanolol and digoxin, and that epanolol does not interfere with the positive inotropic action of digoxin.

Adrenergic beta-Antagonists↗
PubMed2003

Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats.

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40%, v/v) and saline mixture with and without Tween 80 (1 or 10%, v/v). Digoxin oral AUC increased 30 and 61% when dosed in 1% and 10% Tween 80, respectively, compared to control (P < 0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10% v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin.

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha t1/2 beta, AUC, C1) were found in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. The most pronounced changes were those in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i.v.) and nontoxic (10 and 2 mg/kg) doses of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by administration of lethal doses of digoxin, was increased only after the highest dose of gentamicin (100 mg/kg), while after nontoxic or close to therapeutic doses (10 and 2 mg/kg) of gentamicin, the digoxin toxicity was either unchanged or even decreased. Digoxin decreased the nerve-muscle blocking effect of gentamicin on cat ischiadicus-gastrocnemius preparation. The possible mechanisms involved are discussed.

Animals↗
PubMed1996

Effect of diprafenone on the pharmacokinetics of digoxin.

This study was conducted to investigate the effect of diprafenone on the steady-state pharmacokinetics of digoxin. Twelve healthy men, all rapid hydroxylators of debrisoquine, received digoxin (0.5 mg per day over 7 days with a loading dose of 2 x 1 mg) or digoxin and diprafenone (3 x 100 mg per day) in three different phases, without a wash-out period (phase 1, digoxin alone; phase 2, digoxin + diprafenone; phase 3, digoxin alone). Blood and urine samples were collected for pharmacokinetic analyses. Diprafenone caused a statistically significant increase in digoxin trough concentrations [1.4 (SD 0.2) vs 1.6 (0.3) ng.ml-1], AUC(zero)-24 values [41 (7) vs 48 (9) ng.h.ml-1 and Css-max[3.9 (0.6) vs 5.5 (0.9) ng.ml-1]. In all volunteers the parameters tended to return to the original values after administration of diprafenone was discontinued [1.4 (0.3) ng.ml-1, 39 (11) ng.h.ml-1, and 3.9 (1.1) ng.ml-1 for trough concentration, AUC(zero)-24 and Cmax respectively]. The mean relative magnitude of the increase in AUC(zero)-24 and trough concentration values corresponded to the mean relative decrease in the renal clearance of digoxin (in both cases approximately 20%). This suggests that the increase in AUC and Css was caused by reduced renal clearance of digoxin.

Adrenergic Agents↗
PubMed2001

Effect of digoxin noncompliance on hospitalization and mortality in patients with heart failure in long-term therapy: a prospective cohort study.

BACKGROUND: As outpatients with long-term chronic illness often show a high incidence of medication noncompliance, we investigated the influence of digoxin noncompliance on hospitalization, left ventricular ejection fraction, and mortality in outpatients in long-term therapy having congestive heart failure with tachycardia at a rate over 100 beats/min before starting digoxin therapy, but abnormal sinus rhythm. METHODS: Before starting this study, the digoxin compliance/noncompliance of patients was determined by measuring the serum digoxin concentration (SDC). SDC was determined once a month, followed for six consecutive months, and patients were defined as noncompliant if their SDC was zero (0.0 ng/ml) on at least three consecutive occasions. According to SDC data, 218 patients were assigned to the compliant group and 213 patients were assigned to the noncompliant group. All 431 patients received diuretics, angiotensin converting-enzyme inhibitors, or nitrates as well as conventional therapy with digoxin throughout the trial. The duration of follow-up was 72 months. FINDINGS: After 72 months of follow-up, the digoxin noncompliant patients showed significant increases in the number and duration of hospitalizations compared with the compliant patients. The digoxin noncompliant patients had a marked decrease in the left ventricular ejection fraction from 49.1% to 41.8%. The cumulative rate of mortality from any cause in noncompliant patients was twofold higher (15.0%) than in compliant patients (7.8%; risk ratio when noncompliant was compared with compliant: 1.95; 95% confidence interval 1.11, 3.45; P = 0.029) at the 72-month follow-up. The higher mortality in digoxin noncompliant patients was exclusively attributed to worsening heart failure rather than other cardiac and noncardiac causes (risk ratio 2.13; 95% confidence interval 1.12, 4.07; P = 0.033). In addition, multiple regression analyses demonstrated that patient noncompliance as well as lower left ventricular ejection fraction at baseline were significantly involved in increased mortality. CONCLUSION: These results indicate that digoxin noncompliance, at least in part, increases the rate of both hospitalization and mortality due to worsening heart failure in outpatients who have congestive heart failure with tachycardia in long-term therapy.

Aged↗
PubMed1978

The prevention and reversal of digoxin intoxication with specific antibodies.

The formation of digoxin-specific antibodies was induced in sheep by immunization with a digoxin-albumin conjugate. The efficacy of the antibodies was investigated in anesthetized cats. When the digoxin-specific antibodies were administered prophylactically as a gammaglobulin, IgG or F (ab')2 preparation, the dose of digoxin needed to induce ventricular dysrhythmia was significantly greater (p less than 0.001) for the pretreated animals than for the controls. To investigate therapeutic efficacy, the animals were digitalized with digoxin over a period of three days and were given digoxin injections on the fourth day to provoke ventricular tachycardia. Of the control animals, three died before two hours had elapsed and the arrhythmia persisted in the two remaining animals. By contrast, a stable sinus rhythm was restored in all animals which were treated with F (ab')2 fragment of the digoxin-specific antibodies after onset of ventricular tachycardia. The doses of digoxin required to trigger renewed ventricular dysrhythmia in these animals were greater than those required at the start of the experiment. The potential clinical use of digoxin-specific antibodies is discussed in the light of these results and reports in the literature.

Animals↗