PREDICTIVE PERFORMANCE OF 4 PHARMACOKINETIC METHODS FOR CALCULATING DIGOXIN DOSAGE

An evaluation was made of the performance of the Sheiner, Koup, Dobbs and Paulson methods for predicting total body clearance of digoxin in 59 patients with and without congestive heart failure (CHF). The predi cted clearances were then used to predict the steady-state serum conce ntrations of digoxin. Actual serum concentrations were measured at ste ady state following single oral daily doses of digoxin for at least 1 month. Predictive performance was determined for each method by calcul ating the mean prediction error (ME) and the mean squared prediction e rror (MSE). Ninety-five per cent confidence intervals and correlation coefficients were also calculated. The prediction bias and precision o f the methods were compared statistically by calculating the 95% confi dence intervals of the Delta ME and Delta MSE. For patients with CHF, the Sheiner method was the least biased and the most precise for predi cting observed serum levels. For patients without CHF, no significant difference between the Sheiner and Koup methods, and between the Dobbs and Paulson methods were seen, although the former two methods were l ess biased and more precise than the latter two. The Sheiner method wa s used as the basis for evaluating the performance of the three other methods in predicting digoxin clearance from patients with and without CHF. This revealed that the Koup, Dobbs and Paulson methods tended to overpredict clearances in patients with CHF; on the other hand, for p atients without CHF, the Koup method was the least biased and the most precise of the three methods.