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• W3016727251 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 (e.g., 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." @default.
• W3016727251 created "2020-04-24" @default.
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• W3016727251 date "2020-07-01" @default.
• W3016727251 modified "2023-10-16" @default.
• W3016727251 title "Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model" @default.
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• W3016727251 doi "https://doi.org/10.1016/j.apsb.2020.04.007" @default.
• W3016727251 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7252145" @default.
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