Comparison of three lithium dosing methods in 950 "subjects" by computer simulation

This study compared the accuracy of the one-point method (OPM) of Cooper et al., the repeated one-point method (ROPM) using a 12 h initial dosage interval (ROPM-12), and the ROPM using a 24 h initial dosage interval (ROPM-24) for predicting lithium steady-state concentrations after lithium carbonate 600 mg every 12 h. Pharmacokinetic values for elimination rate constant (k), volume of distribution (V), and absorption rate constant (ka) were generated randomly for 950 subjects to produce normally distributed values of the parameters with target means and standard deviations in accordance with values reported in the literature. Errors with a mean of zero and a standard deviation of +/- 5% (SD5%) and +/- 10% (SD10%) were added to the calculated lithium concentrations used in the prediction methods to simulate assay and timing errors. The mean (+/- SD) values generated for k, ka, and V were 0.035 +/- 0.008 (h-1), 0.897 +/- 0.059 (h-1), and 40.97 +/- 5.27 (L), respectively. Prediction errors were smallest with the OPM (SD5%, SD10%) and ROPM-24 (SD5%). There was a significant correlation between k and the prediction error for the OPM (SD5%, SD10%) and the ROPM-24 (SD5%). The OPM was the most accurate of the methods studied; however, it tended to underpredict actual concentrations in subjects with long half-lives.