Concordance of Exposure Changes Because of Renal Impairment Between Results of Dedicated Renal Impairment Studies and Population Pharmacokinetic Predictions

This analysis compared the results from noncompartmental analysis and population pharmacokinetic (PopPK) predictions of exposure changes in patients with renal impairment (RI) for 27 new molecular entities (NMEs) approved between 2000 and 2015. Renal function was identified as a covariate in the fin...

Full description

Saved in:
Bibliographic Details
Published in:Journal of clinical pharmacology 2021-10, Vol.61 (10), p.1324-1333
Main Authors: Ahmed, Mariam A., Kalaria, Shamir N., Younis, Islam R.
Format: Article
Language:English
Subjects:
Area Under Curve
Discordance
Drugs, Investigational - pharmacokinetics
Humans
Metabolic Clearance Rate
Models, Biological
noncompartmental analysis
NONMEM
Patient Acuity
Pharmacokinetics
population pharmacokinetics
Population studies
Renal function
renal impairment
Renal Insufficiency - metabolism
United States
United States Food and Drug Administration
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:This analysis compared the results from noncompartmental analysis and population pharmacokinetic (PopPK) predictions of exposure changes in patients with renal impairment (RI) for 27 new molecular entities (NMEs) approved between 2000 and 2015. Renal function was identified as a covariate in the final PopPK model for 17 NMEs. The final PopPK model was used to simulate (n  =  1000 replicates/individual) the results of a dedicated PK study in subjects with renal impairment. For the majority of NMEs, concordance between observed, and predicted area under the curve (AUC) geometric mean ratio (GMR) was observed (ie, in 17, 11, and 11 NMEs for mild, moderate, and severe renal impairment groups, respectively, the observed and predicted AUC GMR were within the same fold of change). Inclusion of colinear covariates in the PopPK model appeared to be the major driver for the NMEs for which there was discordance. PopPK, when done properly, is a valuable tool for supporting labeling recommendations for subjects with renal impairment.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.1907