Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model.

ABSTRACT: Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of

SUBMITTER: Cui C 

PROVIDER: S-EPMC7252145 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature