Predictive performance of four 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 predicted clearances were then used to predict the steady-state serum concentrations of digoxin. Actual serum concentrations were measured at steady state following single oral daily doses of digoxin for at least 1 month. Predictive performance was determined for each method by calculating the mean prediction error (ME) and the mean squared prediction error (MSE). Ninety-five per cent confidence intervals and correlation coefficients were also calculated. The prediction bias and precision of the methods were compared statistically by calculating the 95% confidence intervals of the delta ME and delta MSE. For patients with CHF, the Sheiner method was the least biased and the most precise for predicting 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 less biased and more precise than the latter two. The Sheiner method was 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 patients without CHF, the Koup method was the least biased and the most precise of the three methods.