Heart failure (HF) causes pathological changes in multiple organs, thus affecting the pharmacokinetics of drugs. The aim of this study was to investigate the pharmacokinetics of candesartan in HF patients while examining significant covariates and their related impact on estimated clearance using a population pharmacokinetics (Pop-PK) modeling approach. Data from a prospective, multicenter study were used. Modeling and simulations were conducted using Nonlinear Mixed-Effects Modeling (NONMEM) and R software. A total of 281 Caucasian patients were included to develop the Pop-PK model. The final model developed for apparent oral clearance (CL/F) included weight, eGFR and diabetes, which partly explained its inter-individual variability. The mean CL/F value estimated was 7.6 L/h (1.7 – 22.6 L/h). Simulations revealed that an important decrease in CL/F (>25%) is obtained with the combination of the factors retained in the final model. Considering these factors, a more individualized approach of candesartan dosing should be investigated in HF patients.This article is protected by copyright. All rights reserved.
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Simon de Denus