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Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients.
Yao, Xueting; Yan, Xiaoyu; Wang, Xiaohan; Cai, Ting; Zhang, Shun; Cui, Cheng; Wang, Xiaoxu; Hou, Zhe; Liu, Qi; Li, Haiyan; Lin, Jing; Xiong, Zi; Liu, Dongyang.
  • Yao X; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Yan X; School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, 999077, China.
  • Wang X; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Cai T; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, 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.
  • Cui C; 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.
  • Wang X; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Hou Z; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Liu Q; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
  • Li H; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Lin J; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
  • Xiong Z; Drug Clinical Trial Center, Peking University Third Hospital, Beijing, 100191, China.
  • Liu D; Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
Eur J Clin Pharmacol ; 77(4): 583-593, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-926186
ABSTRACT

AIMS:

Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure-efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. SUBJECT AND

METHODS:

In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications.

RESULTS:

A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h-1, and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml).

CONCLUSION:

Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics-pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19.
Subject(s)
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Chloroquine / Drug Repositioning / COVID-19 Drug Treatment / Models, Biological Type of study: Reviews Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Eur J Clin Pharmacol Year: 2021 Document Type: Article Affiliation country: S00228-020-03032-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Chloroquine / Drug Repositioning / COVID-19 Drug Treatment / Models, Biological Type of study: Reviews Topics: Variants Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Eur J Clin Pharmacol Year: 2021 Document Type: Article Affiliation country: S00228-020-03032-6