Prediction of clinical irrelevance of PK differences in atorvastatin using PK/PD models derived from literature-based meta-analyses.

ABSTRACT: To support the development of a fixed-dose combination (FDC) of ezetimibe and atorvastatin for the treatment of dyslipidemia, bioequivalence (BE) studies were conducted across a combined dose range (10/10, 10/20, 10/40, and 10/80 mg of ezetimibe/atorvastatin). In the BE trials, all parameters met traditional BE bounds except for atorvastatin peak plasma concentration (Cmax) at two intermediate doses. Literature-based metadata analysis predicted that the observed difference in Cmax between an ezetimibe+atorvastatin FDC and coadministration of these agents translates directly into a non-clinically significant change of <1.2% absolute difference in the percentage lowering of low-density-lipoprotein cholesterol . Both FDC doses were confirmed to be clinically equivalent to coadministration in

SUBMITTER: Vargo R 

PROVIDER: S-EPMC4062834 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature