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Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin
Author(s) -
Storstein Liv
Publication year - 1976
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt19762016
Subject(s) - digitoxin , digoxin , digitalis , pharmacology , medicine , impaired renal function , renal function , hemodialysis , drug , chemistry , endocrinology , heart failure
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 86 Rb 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‐bisdigitoxoside), 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 junction. 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 < 0.0025) and digoxin binding from 23.5% to 15.4% (p < 0.05). In the uremic patient the metabolic pattern of digitoxin tended toward a decrease in protein‐bound metabolites.

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