P. Noertersheuser, S. Ghani, S.Kreis
.
The aim of pharmacokinetic (pk) evaluation is to identify key characteristics of a drug, which allow the characterisation and prediction of the time course of drug effect under physiological and patho-physiological conditions. Based on data obtained in phase I and phase II studies, a mathematical model has been derived which allows prediction of the time course of plasma concentration of a new antithrombotic acting drug, currently in development. To date observed data from about 400 healthy volunteers / patients (3752 samples in all) are included in the database. The objective of the analysis is to verify the suitability of individual pk / pd estimates as prognostic factors for clinical outcome, including efficacy and safety endpoints. Patient studies usually consist of incomplete and sparse data with variation in the number and timing of samples between individuals. For this reason, population based statistical methods, based on nonlinear mixed effect models are employed to obtain individual parameter estimates. In order to address potential issues of bias and robustness of results, model checking and diagnostic procedures are carefully examined. Population based methods are currently implemented in widespread programs such as NONMEM and P-Pharm 1.4. The results obtained with both programs will provide a framework for planning the design of new clinical studies and safe treatment of patients included into these studies. The results of pk evaluation and an overview of the strengths and weaknesses of both programs will be given from the point of view of a user.
Reference: PAGE 7 () Abstr 291 [www.page-meeting.org/?abstract=291]
Poster: poster