Role of Pharmacokinetics in Drug Dosage Adjustment. I. Pharmacologic Effect Kinetics and Apparent Volume of Distribution of Digoxin

Skeletal muscle digoxin binding in patients with renal failure.

“…Finally, the selection of patients in our study may be different from that in the cited studies of the apparent volume of distribution of digoxin in patients with renal failure (Reuning et al, 1973;Szefler & Jusko, 1973;Aronson & Grahame-Smith, 1976). Despite the fact that the glomerular filtration rates were of the same magnitude, the serum electrolyte balance was probably less disturbed in our patients.…”

“…A decrease in the apparent volume of distribution of digoxin has been reported in uraemic patients (Reuning et al, 1973;Szefler & Jusko, 1973;Aronson & Grahame-Smith, 1976). This reduction of the volume of distribution has been considered to indicate either a decrease in the volume of extracellular fluid or decreased binding of digoxin to such quantitatively important tissues as skeletal muscle (Reuning et al, 1973).…”

“…This reduction of the volume of distribution has been considered to indicate either a decrease in the volume of extracellular fluid or decreased binding of digoxin to such quantitatively important tissues as skeletal muscle (Reuning et al, 1973). The aim of the present investigation was to estimate the skeletal muscle digoxin binding in patients with chronic renal failure and to compare it with digoxin binding to skeletal muscle in subjects with normal renal function.…”

Dosage adjustment in renal insufficiency.

“…In addition to the above exceptions there are 'non-renal' ways in which renal failure patients differ from normals. The binding of acidic drugs to plasma albumin is diminished for example (Reidenberg, 1977a); distribution volumes of water soluble drugs like gentamicin are increased (Gyselynck et al, 1971) and of highly tissue-bound drugs like digoxin are reduced (Reuning et al, 1973); elimination by mixed function oxidase may be enhanced and by N-acetylation impaired (Reidenberg, 1977b T,12 (h), rate constant k (h-') and clearance CL (1/h) in patients with severe renal insufficiency (GFR < 10 ml/min). There are special problems in the study of these patients.…”

Digoxin Therapy: Textbooks, Theory and Practice

“…There is at present some controversy over correct loading dose in renal failure between pharmacokineticists, one group of whom believes in lowering the loading dose (Reuning, Sams & Notari, 1973) and one (Wagner, 1974) who believes that the loading dose should be the same as for patients with normal renal function (although the latter agrees that the recommended loading doses in the literature for patients without renal failure are too high); we have observed three patients in renal failure to whom normal or low loading doses were administered, two of whom developed frank toxicity and one equivocal toxicity. We would recommend reducing the loading dose by up to 1/2 in renal failure, augmenting the dose only if the desired therapeutic response is not achieved.…”