Population Pharmacokinetics of Hydroxychloroquine and 3 Metabolites in COVID-19 Patients and Pharmacokinetic/Pharmacodynamic Application.

ABSTRACT: We develop a population pharmacokinetic model for hydroxychloroquine (HCQ) and three of its metabolites (desethylhydroxychloroquine, Des HCQ; desethylchloroquine, DesCQ; and didesethylchloroquine, didesCQ) in COVID-19 patients in order to determine whether a pharmacokinetic (PK)/pharmacodynamic (PD) relationship was present. The population PK of HCQ was described using non-linear mixed effects modelling. The duration of hospitalization, the number of deaths, and poor clinical outcomes (death, transfer to ICU, or hospitalization ≥ 10 d) were evaluated as PD parameters. From 100 hospitalized patients (age = 60.7 ± 16 y), 333 BHCQ and M were available for analysis. The data for BHCQ were best described by a four-compartment model with a first-order input (KA) and a first-order output. For M,

SUBMITTER: Alvarez JC 

PROVIDER: S-EPMC8877570 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature