Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model
Acta Pharmaceutica Sinica B
;
(6): 1216-1227, 2020.
Artículo
en Inglés
| WPRIM
| ID: wpr-828811
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 the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1 750 mg BID, Days 2-5 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1 750 mg and 500 mg, Days 2-3 500 mg BID, Days 4-5 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
Texto completo:
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Índice:
WPRIM (Pacífico Occidental)
Tipo de estudio:
Estudio pronóstico
Idioma:
Inglés
Revista:
Acta Pharmaceutica Sinica B
Año:
2020
Tipo del documento:
Artículo
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