Über die Bindung der Digitaliskörper an die Eiweißstoffe des Blutes

Lendle, L.; Pusch, P.

doi:10.1007/bf01858629

Cited by 24 publications

(4 citation statements)

References 16 publications

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“…Digitoxin and digoxin protein binding is similarly affected by hemodialysis. This does not point to alterations in the metabolic pattern of digitoxin Digitalis and impaired renal function 13 as an important explanation for the observed changes in protein binding, since digoxin is excreted mainly in the unchanged form.16…”

Section: Protein Binding Of Digitalis Glycosidesmentioning

confidence: 91%

Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin

Storstein

1976

Clin Pharma and Therapeutics

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The aim of the present investigation is to study digitoxin and digoxin protein binding in patients with normal renal and hepatic function, in patients with uremia, and in patients under treatment with hemodialysis for renal failure. The binding of digitoxin and cardioactive metabolites to serum proteins was studied using equilibrium dialysis (an in vitro chemical assay) alone and in combination with a modified 86Rb method. The following values for protein binding were found: DT-3 (digitoxin), 95.7%; DT-2 (digitoxigenin-bis-digitoxoside), 96.5%; DT-1 (digitoxigenin-mono-digitoxoside), 98.7%; DT-0 (digitoxigenin), 92.7%; DG-3 (digoxin), 21.2%; DG-2 (digoxigenin-bis-digitoxoside), 16.3%; DG-1 (digoxigenin-mono-digitoxoside), 18.5%; and DG-0 (digoxigenin), 13.3%. In vitro addition of procainamide, phenytoin, heparin, and rifampicillin did not influence the in vitro binding of digitoxin. Protein binding of digitoxin showed small individual variations in patients with normal renal and hepatic function. Uremia per se did not influence the in vitro binding of digitoxin. There were marked changes in digitoxin and digoxin protein binding during an 8-hr hemodialysis, digitoxin binding decreasing from 97.1% to 93.7% (p less than 0.0025) and digoxin binding from 23.5% to 15.4% (p less than 0.05). In the uremic patient the metabolic pattern of digitoxin tended toward a decrease in protein-bound metabolites.

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Section: Protein Binding Of Digitalis Glycosidesmentioning

confidence: 91%

Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin

Storstein

1976

Clin Pharma and Therapeutics

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“…The plasma was first dialyzed against 2 liters of triethylamine-acetic acid buffer at a pH of 9.0, and the dialysate was used in the electrophoretic run (10), which was carried out at 600 v and 95 ma while the plasma was applied to the paper at the rate of 1.5 ml/hour. 30 precipitin arc corresponding to albumin and no evidence of other plasma proteins.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequent investigators (2)(3)(4) demonstrated that the protective action of serum was related to binding of the glycosides by albumin, and that the globulins did not participate in this reaction.…”

Section: Introductionmentioning

confidence: 99%

Binding of digitoxin and some related cardenolides to human plasma proteins

Lukas¹,

Martino²

1969

J. Clin. Invest.

136

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A B S T R A C T Tritium-labeled digitoxin, digitoxigenin, digoxin, and digoxigenin of established purity and chemcal authenticity were used to study the binding of these compounds to human plasma proteins. 97% of digitoxin in plasma was nondialyzable. Continuous flow paper electrophoresis of plasma containing digitoxin and dialysis experiments in which human serum albumin competed for the glycoside with plasma or plasma protein fractions demonstrated that digitoxin was almost exclusively bound by albumin. Equilibrium dialyses revealed that the interaction was characterized by a single binding site on the albumin molecule and an association constant of 9.62 X 10' liter/mole at 370C. At 1VC the association constant was 4.64 X 10' liter/mole. The interaction therefore was endothermic; the gain in enthalpy of 3.5 kcal/mole and the free energy change of -7.06 kcal/ mole was derived from a large change in entropy of 33.8 cal/mole per 'K. The direction of these thermodynamic changes suggested the formation of a hydrophobic bond between digitoxin and albumin. Quenching of the fluorescence of albumin by digitoxin indicated that the conformation of albumin was altered by the binding process.Digitoxigenin, its mono-and didigitoxosides, digoxin, and digoxigenin competed with digitoxn for its binding site on albumin. The affinity of the mono-and didigitoxosides for the site was equal to that of digitoxin, but that of digitoxigenin was only one-third as great. The ability of the digitoxose residues of the glycosides to enhance binding to albumin was also observed with digoxin, Presented in part at the 28th Scientific Sessions of the American Heart Association, Miami Beach, Fla., 16 October 1965.Dr. De Martino was formerly a Postdoctoral Research Fellow of the National Heart Institute.Received for publication 15 November 1968 and in revised form 6 February 1969. which was more extensively bound by the protein than digoxigenin.At concentrations of 2 jg/ml or less in plasma, only 23% of digoxin was bound. Albumin, which interacted with digoxin with an apparent association constant of 9 X 102 liter/mole at 370C, was entirely responsible for the binding. Lowering the temperature from 370 to 1VC decreased the fraction of digoxin bound to albumin by two-thirds.The marked difference in avidity of digitoxin and digoxin for serum albumin is reflected by the higher plasma concentrations, lower rate of urinary excretion, and longer half-time of digitoxin as compared to those of digoxin when these compounds are administered to man.

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“…The protective effect of serum is due to glycoside binding to serum 'proteins (Hoekstra, 1931;, Lendle and Pusch, 1935); mainly to serum albumin (Evered, 1972;Farah, 1944;Fawaz and Farah, 1944;Lukas and De Martino, 1969), Digitalis glycosides are also bound by y-globulin (Kuschinsky, 1969;Lukas and De Martino, 1969;Scholtan et ai., 1966), but addition of physiological amounts of y-globulin to human albumin samples does not affect the binding of digitoxin (Storstein,I 976a). :…”

Section: Protein Binding Of Cardiac Glycosidesmentioning

confidence: 97%

Protein Binding of Cardiac Glycosides in Disease States

Storstein

1977

Clinical Pharmacokinetics

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Digitoxin in 97% bound to serum albumin and digoxin only to the extent of 24%. Hypoalbuminaemia significantly changes the protein binding of digoxin in Kwashorkor serum and the binding of digitoxin in patients with chronic active hepatitis and the nephrotic syndrome. Sprue patiens with normal albumin values have normal binding of digitoxin. Preliminary data in patients with thyrotoxicosis and myxoedema show digitoxin binding within the normal range. The effect of uraemia per se on digitoxin binding is controversial as both normal and slightly decreased values have been reported. In uraemic patients on treatment with haemodialysis, heparin administration has been shown to be a powerful serum binding displacing agent for both digitoxin and digoxin, the mechanism probably being a heparin-induced release of free fatty acids. Patients with a significant decrease in serum protein binding of digitoxin or digoxin should be maintained on a total serum concentration lower than usually considered within the therapeutic range.

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Über die Bindung der Digitaliskörper an die Eiweißstoffe des Blutes

Cited by 24 publications

References 16 publications

Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin

Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin

Binding of digitoxin and some related cardenolides to human plasma proteins

Protein Binding of Cardiac Glycosides in Disease States

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