0. Petricoul(1,2), A. Iliadis(1), L. Claret(1). C. Puozzo(2)
(1)Laboratoire dc Pharmacocinétique, Faculté de Pharmacie, 27 bld Jean Moulin, 13385 Marseille Cedex 5; (2)Centre de Pharmacocinétique, Pierre Fabre Médicament, Bel Air de Campans, 81106 Caslres Cedex
The aim of the study was to assess the inter-individual variability of F2207, a new antidepressant drug with an original structure developed by Pierre Fabre Medicament. Pharmacokinetic data were extracted from phase I/II of its development. Individual kinetics were sufficiently documented to allow estimation of individual pharmacokinetic parameters. Population values were then estimated with reference to Standard Two Stage method. Information theory, supplied the information measure :
This new concept in Population Pharmacokinetics was proposed to check the magnitude of this dispersion of the joint probability density function of Pharmacokinetic and Pharmacodynamic parameters and covariates. In particular, this tool was used to solve four problems, in order to have a reliable description of variability :
- (i) detection of outlying data
- (ii) minimum number of patterns (iii) detection of sub-populations (iiii) screening of covariates.
Applying this tool to F2207 data showed 10 subjects as outliers over 93 healthy volunteers (due to a lack of data in absorption phase). They were separately analysed. Then, results showed that 55 healthy volunteers were actually sufficient to describe the variability of F2207. Infants, elderly and subjects with renal insufficiency exhibited atypical pharmacokinetics (increase in variability related to drop in 1, with reference to healthy volunteers). Body weight was found to be determinant for Vdss.
Reference: PAGE 3 (1994) Abstr 848 [www.page-meeting.org/?abstract=848]
Poster: poster