Population Pharmacokinetics of Candesartan in Patients with Chronic Heart Failure

• DOI: 10.1111/cts.12842
• Publication Date: 2020-07-23T17:52:17Z
• Authors: Imad Kassem; Steven Sanche; Jun Li; Guillaume Bonnefois; Marie‐Pierre Dubé; Jean‐Lucien Rouleau; Jean‐Claude Tardif; Michel White; Jacques Turgeon; Fahima Nekka; Simon de Denus
• Keywords: Candesartan; NONMEM; Population Pharmacokinetics

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