Pharmacokinetics of digoxin in the elderly [proceedings]

Abstract

Pharmacokinetics of a number of drugs are altered in the elderly (Crooks, O'Malley & Stevenson, 1976). A reduction in digoxin excretion related to decreased renal function has been shown in the elderly (Ewy, Kapadia, Yao, Lullin & Marcus, 1969) and is an important determinant of added susceptibility to unwanted effects of this drug. Alterations in absorption or distribution of digoxin would also affect dose requirements in these patients. In this study we compared digoxin pharmacokinetics in elderly and younger patients with particular emphasis on absorption and distribution. Observations were made in seven elderly (aged 72-91 years) and six younger (aged 34-61 years) patients, in whom digoxin was indicated for its inotropic effect. Elderly patients received digoxin 0.25 mg and younger patients digoxin 0.5 mg R.J.P. (PROC.) A both intravenously and orally with at least 2 weeks between doses. Blood samples for estimation of plasma digoxin concentrations by radioimmunoassay were withdrawn before, at 15, 30, 45 and 60min and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36 and 48 h after administration of digoxin.The results are shown in Table 1. Peak digoxin concentrations were attained earlier in the younger subjects (P < 0.05, Wilcoxon's rank sum test). Digoxin half-life after both routes was significantly longer in the elderly. The extent of absorption calculated as the ratio of area under the plasma concentration-time curves after oral and intravenous administration was not significantly different in the young and old subjects. The elderly had a significantly smaller apparent volume of distribution but after correction for weight the difference was not significant. Plasma clearance of digoxin (both absolute and weight corrected) was significantly lower in the older patients.Thus the rate of absorption of digoxin is slowed in elderly patients but the extent of absorption is unchanged. Older patients have a smaller volume of distribution of digoxin which probably reflects their decreased lean body mass.

Serum Concentration Monitoring of Cardiac Glycosides

“…This was despite 92% of the patients from group A having a CLtR between 15 and 60 ml/min, compared with 48% of group B. Cusack et al (1978) showed that the rate of absorption of digoxin was slower in 7 elderly patients (aged 72 to 91 years) than in 6 younger ones (aged 34 to 61 years), but the extent was similar. Strenuous or sustained exercise transiently reduces serum digoxin concentrations in younger adults, but it is unlikely that the concentrations of the elderly patients were lowered by this mechanism.…”

Adverse Drug Reactions Among the Elderly: A Reassessment

“…The associated physiologic changes include decreases in total body water and lean body mass (23)(24)(25), baroreceptor sensitivity (26)(27)(28), renal blood flow and glomerular filtration rate (29,30), liver mass and enzyme activity (31,32), and the protein binding of drugs (33). In the past, these physiologic transformations have been correlated with alterations in the metabolism and actions of drugs such as digoxin and the benzodiazepines (34)(35)(36)(37)(38). However, our knowledge of the effect of aging on the pharmacokinetics and pharmacodynamics of most drugs used by the elderly (e.g., analgesics, antihypertensive agents) is limited.…”

Prescribing digoxin in geriatric units: The unexplained variability in dosage requirements

“…Impaired absorption of drugs such as levodopa (Wade et al 1973), which depend for their absorption on an active transport mechanism, has previously been reported in the elderly, but clinically important impaired absorption of a drug which is absorbed by simple diffusion has not. Cusack et al (1978) showed that the rate of absorption of digoxin was slower in seven elderly patients (aged 72 to 91 years) than in six younger ones (aged 34 to 61 years), but the extent was similar.…”