PREDICTIVE PERFORMANCE OF POPULATION PHARMACOKINETIC PARAMETERS OF TIANEPTINE AS APPLIED TO PLASMA-CONCENTRATIONS FROM A POSTMARKETING STUDY

The predictive ability of population pharmacokinetic parameters of tia neptine, obtained from a mixed effect analysis of pre-marketing pharma cokinetic studies, was evaluated using tianeptine plasma concentration s obtained during a large multi-center post-marketing surveillance stu dy. The mean prediction error was 7.8 ng . ml-1 and the root mean squa re prediction error was 52.1 ng/ml when initial estimates of populatio n 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 p ost-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 param eters obtained from pre-marketing data may not accurately predict drug concentrations in patients receiving the drug in the post-marketing s etting. Once the population parameters are updated to reflect data fro m the post-marketing period, the predictive ability of the data-base i ncreases, but substantial variability in the prediction error remains.