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 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.