Prediction of Clinical Irrelevance of PK Differences in Atorvastatin Using PK/PD Models Derived From Literature-Based Meta-Analyses

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 tr...

Full description

Saved in:
Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2014-07, Vol.96 (1), p.101-109
Main Authors: Vargo, R, Adewale, A, Behm, M O, Mandema, J, Kerbusch, T
Format: Article
Language:English
Subjects:
Atorvastatin Calcium
Azetidines - pharmacokinetics
Azetidines - pharmacology
Biological and medical sciences
Cholesterol, LDL - blood
Drug Therapy, Combination
Ezetimibe
Heptanoic Acids - pharmacokinetics
Heptanoic Acids - pharmacology
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Medical sciences
Meta-Analysis as Topic
Models, Biological
Pharmacology. Drug treatments
Pyrroles - pharmacokinetics
Pyrroles - pharmacology
Therapeutic Equivalency
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:0009-9236
1532-6535
DOI:10.1038/clpt.2014.66