Clinical Pharmacokinetics of Digoxin

Abstract

About 70 to 80% of an oral dose of digoxin is absorbed, mainly in the proximal part of the small intestine. The degree of binding to serum albumin is 20 to 30%. Digoxin is extensively distributed in the tissues, as reflected by the large volume of distribution. High concentrations are found in the heart and kidneys, but the skeletal muscles form the largest digoxin storage. The half-life of elimination in healthy persons varies between 26 and 45 hours. The main route of elimination is renal excretion of digoxin, which is closely correlated with the glomerular filtration rate. In addition, some tubular secretion and perhaps tubular reabsorption occurs. Nearly all of the digoxin in the urine is excreted unchanged, with a small part as active metabolites. The clinical significance of dihydrodigoxin as a metabolite remains to be resolved. About 25 to 28% of digoxin is eliminated by nonrenal routes. Biliary excretion may rise up to 30% of a given dose, but the enterohepatic cycle seems to be of minor importance. The pharmacodynamic effects of digoxin, including toxic symptoms, are correlated with the uptake of digoxin in the heart after a single dose and with the steady state serum digoxin concentration during maintenance therapy. Impaired kidney function is the most important condition with an influence on the pharmacokinetics of digoxin. In addition to the renal clearance of creatinine, the biovailability of the digoxin formulation used, the volume of distribution, the amount of extrarenal clearance, body weight and serum albumin concentration, are other factors which may modify the serum level of digoxin. Certain drug interactions may also occur during the absorptive phase. Exact prediction of serum digoxin concentrations by various dosage calculations has not succeeded. Since many factors may influence the sensitivity of the myocardium to digoxin, measurement of serum digoxin levels in only one, but a useful criterion, when making clinical decisions about adjustment of digoxin dosage.

Appropriateness of digoxin level monitoring in a childrens hospital

“…These findings are similar to those reported in other studies (Pinsky et al, 1979;Halkin et al, 1978) and reflect the lower capacity for renal excretion of digoxin by the relatively immature kidney (Iisalo, 1977). In neonates renal excretion accounts for 57 to 80% of digoxin elimination, in the first few months after birth renal blood flow and glomerular filtration rate increase and there is a significant gain in renal function, leading to a gradual increase in digoxin excretion.…”

“…The halflife of digoxin is longer in infants less than 4 months of age than in adults, mainly because renal function is not fully developed (Halkin et al, 1978;Iisalo, 1977;Wettrell, 1977;Suematsu et al, 1999). In adults receiving a fixed daily dose steady state is achieved after 6 to 7.5 days, whereas in neonates this still need more evidences to confirm, hence we have to use the adult standard, and a recommended time is need to establish for children.…”

Inhibitory effects of digoxin and ouabain on aldosterone synthesis in human adrenocortical NCI‐H295 cells

“…Since no significant cytotoxicity was observed at 10 À6 M digoxin or ouabain, the digoxinor ouabain-induced decrease of aldosterone or cortisol release was not associated with cytotoxicity. These results demonstrate that digoxin or ouabain inhibits the aldosterone or cortisol release via reduction of P450c11AS or P450c11b and P450scc activities, inhibition of StAR and P450scc protein expression, suppression of P450c11AS mRNA expression, and attenuation of Ca Digoxin, a glycosylated steroid-like digitalis glycoside isolated from foxglove, is administered to patients with congestive heart failure and cardiac arrhythmia (Iisalo, 1977). Actions of digitalis include positive inotropic effect on cardiac muscle through an inhibition of the Na þ /K þ -ATPase and a consequence of Na þ -Ca 2þ exchange to an increase of intracellular calcium concentration (Hougen and Smith, 1978).…”

Effect of itraconazole on the pharmacokinetics of digoxin in guinea pigs

“…The findings on the excretion of DGX suggest that ITZ reduced both the biliary and urinary excretion of DGX (Figures 2 and 3). On the other hand, DGX was reported in man to be excreted largely in urine as the unchanged form after iv administration of DGX, and its urinary recovery was 60 -80% [14,15]. Sheiner et al [16] reported that the total body, renal and metabolic clearances of DGX were 2.909 1.0, 1.64 90.50 and 0.79090.460 mL/min/kg (mean9…”