Population‐Based Investigation of Relative Clearance of Digoxin in Japanese Patients by Multiple Trough Screen Analysis: An Update

Abstract

The steady‐state concentrations of digoxin at trough levels were studied to reestablish the role of patient characteristics in estimating doses for digoxin using routine therapeutic drug‐monitoring data. The data (n = 548) showing steady‐state serum concentrations of digoxin after repetitive oral administration in 385 hospitalized patients were analyzed using NONMEM, a computer program designed to analyze pharmacokinetics in study populations by allowing pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished with a simple steady‐state pharmacokinetic model. The effect of a variety of developmental and demographic factors on the clearance of digoxin was investigated. Estimates generated by NONMEM indicated that clearance of digoxin was influenced by the demographic variables of age, total body weight, serum creatinine, estimated creatinine clearance, gender, the coadministration of spironolactone, the presence or absence of congestive heart failure, and the administration of a half‐tablet. The interindividual variability in the clearance of digoxin was modeled with proportional error with an estimated coefficient of variation of ∼22%; the residual variability was ∼25.0%. An a priori method, based on the value for clearance of digoxin obtained by NONMEM analysis, was proposed as a useful adjunct for the prediction of the steady‐state concentration of digoxin at trough level as a function of the maintenance dose of digoxin.