Predictive performance of population pharmacokinetic parameters of tianeptine as applied to plasma concentrations from a post-marketing study

Summary

The predictive ability of population pharmacokinetic parameters of tianeptine, obtained from a mixed effect analysis of pre-marketing pharmacokinetic studies, was evaluated using tianeptine plasma concentrations obtained during a large multi-center post-marketing surveillance study.

The mean prediction error was 7.8 ng·ml⁻¹ and the root mean square prediction error was 52.1 ng/ml when initial estimates of population pharmacokinetic parameters were used to predict drug concentrations in one half of the post-marketing data. When the population parameters were revised to reflect the data collected in the first half of the post-marketing study, the mean prediction error was reduced to −3.2 ng·ml⁻¹ and the root mean square prediction error was reduced to 29.5 ng·ml⁻¹.

These results suggest that population pharmacokinetic parameters obtained from pre-marketing data may not accurately predict drug concentrations in patients receiving the drug in the post-marketing setting. Once the population parameters are updated to reflect data from the post-marketing period, the predictive ability of the database increases, but substantial variability in the prediction error remains.