Digoxin in the elderly: Pharmacokinetic consequences of old age

Abstract

A study of single-dose digoxin kinetics was performed in 6 young and 7 elderly patients. The rate of absorption, determined by the time to peak concentration after an oral dose, was more rapid in the younger group. The extent of absorption, as measured by comparison of the area under the plasma concentration/time curve after oral and intravenous administration, was similar in both groups. Mean plasma half-life was longer and individual values were more variable in the elderly patients. The absolute apparent volume of distribution was reduced in the older patients and correlated inversely with age. When corrected for weight, however, the difference in the apparent volume of distribution did not approach significance. Both absolute and weight-corrected values for plasma clearance of digoxin were reduced in the elderly subjects.

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

“…However, the time to peak plasma concentrations is prolonged with advancing age from a mean of 38 h in younger subjects to 69 h in elderly subjects [60]. Therefore, the time to reach steady-state plasma concentrations increases from 7 to 12 days in elderly subjects.…”

“…Gentamicin, digoxin, ethanol, theophylline, and cimetidine fall into this category [58][59][60]. Loading doses of digoxin need to be reduced to accommodate these changes [60].…”

“…The volume of distribution is decreased in elderly patients. As a result, loading doses should be reduced by approximately 20% [60].…”

“…Because digoxin is cleared mainly through the kidneys and digoxin clearance is proportional to creatinine clearance [98], the systemic clearance of digoxin is reduced with age [60]. As clearance is the main determinant of the maintenance dose, the daily dose of digoxin should be reduced.…”

Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

“…Elderly and Renal failure Age-related changes in the pharmacokinetics of digoxin contribute signiticantly to the increased predisposition of the elderly to toxicity. Age-related differences in absorption, protein binding, and extrarenal clearance of digoxin are not well defined but do not appear to be clinically important [25]. A major pharmacokinetic factor contributing to the increased predisposition to digoxin toxicity relates to the change in volume of distribution of digoxin with aging [26].…”