Interindividual differences in the pharmacokinetics of digitoxin and digoxin during long-term treatment

Haustein, Knut-Olaf

doi:10.1007/bf00558383

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Consistent with prev ous studies of digitoxin (Perrier et al, 1977;Ochs et al, 1980b;Haustein, 1981;Vohringer & Rietbrock, 1978), elimination half-life is very long, averaging 8 days in the present study. Digitoxin volume of distribution averaged 0.76 1/kg.…”

Section: Multiple-dose Kineticssupporting

confidence: 92%

Digitoxin accumulation.

Ochs¹,

Pabst²,

and³

et al. 1982

Brit J Clinical Pharma

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1 Nine healthy volunteers received single 1 mg intravenous doses of digitoxin, following which serum digitoxin concentrations were measured at multiple points in time over the next 14 days. 2 Mean kinetic variables for digitoxin were: volume of distribution, 0.761/kg; elimination half-life, 8 days; total clearance, 0.049 ml min-kg-'. 3 After a drug-free interval of at least 4 months, subjects took 0.07 mg of oral digitoxin daily for 28 consecutive days. Serum digitoxin concentrations were measured during the period of dosage and in the 21 day post-dosage washout. 4 Digitoxin accumulation was slow, proceeding with a mean half-life (7.9 days) that was nearly identical to the single-dose half-life. However, the two were not significantly correlated. 5 Mean observed steady-state serum concentrations (15.4 ng/ml) also were nearly identical to those predicted from the single-dose study (15.3 ng/ml), but again the two were not significantly correlated. 6 Steady state is very slowly attained after initiation of maintenance therapy with digitoxin. The kinetic data suggest that a loading dose on the average should be 12 times the maintenance dose.

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Section: Multiple-dose Kineticssupporting

confidence: 92%

Digitoxin accumulation.

Ochs¹,

Pabst²,

and³

et al. 1982

Brit J Clinical Pharma

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show abstract

“…The plasma half-life after administration of radioactive labelled digitoxin was shown to be about 77-234 h (mean 138 h) [33]. In a status of normal liver and kidney function, 60% of digitoxin is eliminated via urine, about half of it as conjugated metabolites, and about 40% is excreted via faeces, partly secreted via bile and partly directly through the mucosal wall [34].…”

Section: Eliminationmentioning

confidence: 99%

“…When kidney function is impaired and renal elimination of digitoxin is reduced, this is compensated by increased metabolization and excretion via the faeces [36,37]. Several authors reported a reduced half-life of digitoxin in patients with kidney malfunction rather than a prolonged one as compared with patients with normal renal function [29][30][31][32][33][34][35][36][37][38][39][40][41]. Also, patients with hepatic insufficiency or with hepatic and renal malfunction showed no significant changes in elimination half-life [20,42].…”

Section: Eliminationmentioning

confidence: 99%

Treatment of congestive heart failure – current status of use of digitoxin

Belz¹,

Breithaupt-Grögler²,

Osowski

2001

Eur J Clin Investigation

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Digitalis glycosides exert a positive inotropic effect, i.e. an increase in myocardial contractility associated with a prolongation of relaxation period, and glycosides lower the heart rate (negative chronotropic), impede stimulus conduction (negative dromotropic) and promote myocardial excitability (positive bathmotropic). They seem to influence the activities of both the vagal and the sympathetic systems. Digitalis glycosides that belong to different substance classes are closely comparable concerning pharmacodynamics but differ substantially in regard to pharmacokinetics. Digoxin and its derivatives are less lipophilic, show lower protein binding and shorter half‐life, are mainly eliminated via the kidney and accumulate rather rapidly in cases of insufficient kidney function. Digitoxin is highly lipophilic and extensively bound to plasma proteins, has a longer half‐life, is mainly eliminated in the metabolized state via urine and faeces and does not accumulate in kidney dysfunction. As a result of a more stable pharmacokinetic profile, the incidence of toxic side effects seems to be lower with digitoxin than with digoxin. Since the beginning of the 1990s, the antagonists of the RAAS qualified as the standard treatment for congestive heart failure, often in combination with diuretics, vasodilators or β‐antagonists. However, the important role of digitalis glycosides as therapeutic comedication or alternative was never denied, especially in atrial fibrillation with tachycardia. The PROVED and RADIANCE trials proved a detrimental effect of the withdrawal of digoxin therapy on exercise capacity, left‐ventricular ejection fraction and clinical symptoms. The DIG trial revealed that digoxin comedication in sinus rhythm patients with congestive heart failure was associated with a lower morbidity (as taken from death or hospitalization because of worsening heart failure) and an unchanged overall mortality – being a unique feature among the available inotropic drugs. Comparable studies for digitoxin have not yet been performed but, because of its higher pharmacological stability, it might well be associated with even more advantages in this regard than digoxin.

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D

Seyffart¹

1991

Drug Dosage in Renal Insufficiency

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Interindividual differences in the pharmacokinetics of digitoxin and digoxin during long-term treatment

Cited by 8 publications

References 16 publications

Digitoxin accumulation.

Digitoxin accumulation.

Treatment of congestive heart failure – current status of use of digitoxin

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