The pharmacokinetics of different cardiac glycosides are altered by renal dysfunction in different ways, depending on their basic pharmacokinetic properties.Digoxin: The linearity of digoxin pharmacokinetics is unchanged by renal dysfunction, as is the bioavailability. Protein binding may be slightly reduced, but the change is of no clinical significance. The apparent volume of distribution is reduced by one-third to onehalf, the change being roughly proportional to the degree of renal impairment. The significance of this change in terms of adjustment of the loading dose is controversial. I believe that the initial oral loading dose should be reduced from 15 pg/kg to 10 pg/kg in renal dysfunction, and supplemented only if there is evidence of a lack of response and no evidence of toxicity.The renal clearance of digoxin is reduced in renal dysfunction and becomes very closely related to the measured creatinine clearance at values of creatinine clearance below 30 ml/ min. As a result, the renal elimination rate constant, and therefore the fraction of the total body load lost per day via the kidneys, falls in renal dysfunction. In contrast, the non-renal clearance of digoxin is probably unaffected. However, because of the fall in apparent volume of distribution the non-renal elimination rate constant rises slightly, accounting for the slight increase in faecally excre.ted digoxin in renal dysfunction. This rise in the non-renal fractional daily loss is not sufficient to counteract the fall in renal fractional daily loss and digoxin maintenance dosages at steady-state need to be reduced. For this purpose the creatinine clearance acts as an initial guide to the extent of the expected reduction in dose, but doses altered on this basis should be regarded as first approximations to the correct dose, and the dose subsequently readjusted according to the patient's clinical response, using the plasma digoxin concentration as a guide. It must be remembered, however, that because of technical problems with digoxin radioimmunoassay in renal dysfunction, and because of the difficulty in interpretation of the result, the plasma digoxin concentration in renal dysfunction is of less value than it is in normal renal function. The overall half-life of digoxin is prolonged in renal dysfunction and it therefore takes longer for a steady-state to be reached during maintenance dose therapy without a loading dose, and longer for toxicity, when it occurs, to resolve.Negligible amounts of digoxin are removed from the body by dialysis procedures. A transplanted kidney retains its ability to handle digoxin, and after transplantation the pharmacokinetics of digoxin return towards normal, depending on the overall improvement in renal function achieved.Digitoxin: There are technical problems with the measurement of digitoxin because of the need to separate digitoxin and its metabolites chromatographically before using the measurement techniques commonly applied. Such separation has not always been carried out, and this makes the interpretation ...