Predictive performance of population pharmacokinetic parameters of tianeptine as applied to plasma concentrations from a post-marketing study.
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 data-base increases, but substantial variability in the prediction error remains.
Grasela
T H
TH
Center for Pharmacoepidemiology Research, University at Buffalo, New York.
Fiedler-Kelly
J B
JB
Salvadori
C
C
Marey
C
C
Jochemsen
R
R
Loo
H
H
D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D017891:Pharmacoepidemiology; D011237:Predictive Value of Tests; D011358:Product Surveillance, Postmarketing; D013841:Thiazepines / Q000097:blood* / Q000493:pharmacokinetics; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine