Population pharmacokinetic and pharmacodynamic modelling of NS2330 and its major metabolite in Alzheimer's disease [Elektronische Ressource] / von Thorsten Lehr

Dissertationzur Erlangung des akademischen Gradesdoctor rerum naturalium (Dr.rer.nat.)Vorgelegt derMathematisch-Naturwissenschaftlich-Technischen Fakultätder Martin-Luther-Universität Halle-Wittenbergvon Thorsten Lehrgeb. am 05.02.1977 in HanauGutachter:1. Prof. Dr. Charlotte Kloft2. Prof. Dr. Reinhardt Neubert3. Prof. Dr. Inaki TroconizHalle (Saale), 19. Juli 2006urn:nbn:de:gbv:3-000010896[http://nbn-resolving.de/urn/resolver.pl?urn=nbn%3Ade%3Agbv%3A3-000010896]Meiner Mutterin Liebe und Dankbarkeitgewidmet.This thesis aims to contribute to a comprehensive characterisation of the pharmacokinetics(PK) and pharmacodynamics (PD) of NS2330, a new compound under clinical developmentfor Alzheimer’s disease (AD), and its major metabolite M1 using the population PK/PD mo-delling approach. Several PK and PD development questions were investigated in six differentmodelling projects. The population PK properties of NS2330 and its metabolite were exploredin healthy volunteers and AD patients within projects I and II. The PK between healthy vol-unteers and AD patients were comparable. Low clearances and large volumes of distributionsresulted in long terminal half-lives of more than 200 h for both compounds.