Related Experiment Video
Updated: Jun 28, 2026

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Comparison of model-based tests and selection strategies to detect genetic polymorphisms influencing pharmacokinetic
Julie Bertrand1, Emmanuelle Comets, France Mentre
1UFR de Medecine-Site Bichat, UMR 738 INSERM Paris Diderot, Paris, France. julie.bertrand@bichat.inserm.fr
Abstract:
We evaluate by simulation three model-based methods to test the influence of a single nucleotide polymorphism on a pharmacokinetic parameter of a drug: analysis of variance (ANOVA) on the empirical Bayes estimates of the individual parameters, likelihood ratio test between models with and without genetic covariate, and Wald tests on the parameters of the model with covariate. Analyses are performed using the FO and FOCE method implemented in the NONMEM software. We compare several approaches for model selection based on tests and global criteria. We illustrate the results with pharmacokinetic data on indinavir from HIV-positive patients included in COPHAR 2-ANRS 111 to study the gene effect prospectively. Only the tests based on the EBE obtain an empirical type I error close to the expected 5%. The approximation made with the FO algorithm results in a significant inflation of the type I error of the LRT and Wald tests.
Related Concept Videos
Pharmacogenetics of Drug Metabolism: Overview
Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Principles of Pharmacogenetics: Types of Genetic Variants
Analysis of Population Pharmacokinetic Data
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

