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Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model.
Cui, Cheng; Zhang, Miao; Yao, Xueting; Tu, Siqi; Hou, Zhe; Jie En, Valerie Sia; Xiang, Xiaoqiang; Lin, Jing; Cai, Ting; Shen, Ning; Song, Chunli; Qiao, Jie; Zhang, Shun; Li, Haiyan; Liu, Dongyang.
  • Cui C; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Zhang M; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Yao X; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Tu S; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Hou Z; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Jie En VS; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Xiang X; Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
  • Lin J; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, HwaMei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo 315010, China.
  • Cai T; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, HwaMei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo 315010, China.
  • Shen N; Department of Respirator, Peking University Third Hospital, Beijing 100191, China.
  • Song C; Department of Orthopedics, Peking University Third Hospital, Beijing 100191, China.
  • Qiao J; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
  • Zhang S; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, HwaMei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo 315010, China.
  • Li H; Drug Clinical Trial Center, Peking University Third Hospital, Beijing 100191, China.
  • Liu D; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China.
Acta Pharm Sin B ; 10(7): 1216-1227, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-88718
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Acta Pharm Sin B Year: 2020 Document Type: Article Affiliation country: J.apsb.2020.04.007

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: Acta Pharm Sin B Year: 2020 Document Type: Article Affiliation country: J.apsb.2020.04.007