Multiple single nucleotide polymorphism analysis using penalized regression in nonlinear mixed-effect pharmacokinetic models

Abstract

CONTEXT: Studies on the influence of single nucleotide polymorphisms (SNPs) on drug pharmacokinetics (PK) have usually been limited to the analysis of observed drug concentration or area under the concentration versus time curve. Nonlinear mixed effects models enable analysis of the entire curve, even for sparse data, but until recently, there has been no systematic method to examine the effects of multiple SNPs on the model parameters. OBJECTIVE: The aim of this study was to assess different penalized regression methods for including SNPs in PK analyses. METHODS: A total of 200 data sets were simulated under both the null and an alternative hypothesis. In each data set for each of the 300 p..