POPULATION-BASED INVESTIGATION OF RELATIVE CLEARANCE OF DIGOXIN IN JAPANESE PATIENTS BY MULTIPLE TROUGH SCREEN ANALYSIS - AN UPDATE

The steady-state concentrations of digoxin at trough levels were studi ed to reestablish the role of patient characteristics in estimating do ses for digoxin using routine therapeutic drug-monitoring data. The da ta (n = 548) showing steady state serum concentrations of digoxin afte r repetitive oral administration in 385 hospitalized patients were ana lyzed using NONMEM, a computer program designed to analyze pharmacokin etics in study populations by allowing pooling of data. Analysis of th e pharmacokinetics of digoxin was accomplished with a simple steady-st ate pharmacokinetic model. The effect of a variety of developmental an d demographic factors on the clearance of digoxin was investigated. Es timates generated by NONMEM indicated that clearance of digoxin was in fluenced by the demographic variables of age, total body weight, serum creatinine, estimated creatinine clearance, gender, the coadministrat ion of spironolactone, the presence or absence of congestive heart fai lure, and the administration of a half-tablet. The interindividual var iability in the clearance of digoxin was modeled with proportion error with an estimated coefficient of variation of similar to 22%; the res idual variability was similar to 25.0%. An a priori method, based on t he value for clearance of digoxin obtained by NONMEM analysis, was pro posed as a useful adjunct for the prediction of the steady-state conce ntration of digoxin at trough level as a function of the maintenance d ose of digoxin.