Application of the extended clearance concept classification system (ECCCS) to predict the victim drug-drug interaction potential of statins
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3386203
Author(s) Kunze, Annett; Poller, Birk; Huwyler, Jörg; Camenisch, Gian
Author(s) at UniBasel Huwyler, Jörg
Year 2015
Title Application of the extended clearance concept classification system (ECCCS) to predict the victim drug-drug interaction potential of statins
Journal Drug Metabolism and Personalized Therapy
Volume 30
Number 3
Pages / Article-Number 175-88
Abstract During drug development, it is an important safety factor to identify the potential of new molecular entities to become a victim of drug-drug interactions (DDIs). In preclinical development, however, anticipation of clinical DDIs remains challenging due to the lack of in vivo human pharmacokinetic data. We applied a recently developed in vitro-in vivo extrapolation method, including hepatic metabolism and transport processes, herein referred to as the Extended Clearance Concept Classification System (ECCCS). The human hepatic clearances and the victim DDI potentials were predicted for atorvastatin, cerivastatin, fluvastatin, lovastatin acid, pitavastatin, pravastatin, rosuvastatin, and simvastatin acid. Hepatic statin clearances were well-predicted by the ECCCS with six out of eight clearances projected within a two-fold deviation to reported values. In addition, worst-case DDI predictions were projected for each statin. Based on the ECCCS class assignment (4 classes), the mechanistic interplay of metabolic and transport processes, resulting in different DDI risks, was well-reflected by our model. Furthermore, predictions of clinically observed statins DDIs in combination with relevant perpetrator drugs showed good quantitative correlations with clinical observations. The ECCCS represents a powerful tool to anticipate the DDI potential of victim drugs based on in vitro drug metabolism and transport data.
Publisher de Gruyter
ISSN/ISBN 2191-0162
edoc-URL http://edoc.unibas.ch/40829/
Full Text on edoc No
Digital Object Identifier DOI 10.1515/dmdi-2015-0003
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/25996489
ISI-Number BCI:BCI201500713412
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.430 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
07/08/2020