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. 2020 Sep 3;17(9):e1003252.
doi: 10.1371/journal.pmed.1003252. eCollection 2020 Sep.

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology

Nicholas J White  1   2 , James A Watson  1   2 , Richard M Hoglund  1   2 , Xin Hui S Chan  1   2   3 , Phaik Yeong Cheah  1   2 , Joel Tarning  1   2
Affiliations

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology

Nicholas J White et al. PLoS Med. .

Erratum in

Abstract

Nicholas White and coauthors discuss chloroquine and hydroxychloroquine pharmacology in the context of possible treatment of SARS-CoV-2 infection.

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Conflict of interest statement

NJW is a member of the PLoS Medicine Editorial Board. The authors declare that no other competing interests exist.

Figures

Fig 1
Fig 1. The metabolism of chloroquine and hydroxychloroquine.
The red stars indicate chiral centres.
Fig 2
Fig 2. Example of a general whole-blood or plasma concentration-time profile for chloroquine or hydroxychloroquine.
Fig 3
Fig 3. Relationship between whole-blood concentrations of chloroquine + desethyl metabolite (μM) measured by UV-spectrophotometry on admission in self-poisoning, and outcome.
The data are from all patients studied prospectively from [93, 109, 111] (n = 258). The 95% nonparametric bootstrap confidence intervals are shown by the vertical lines. No deaths were observed for admission concentrations less than 15 μM. Raw data used to produce this image are provided in S1 File.
Fig 4
Fig 4. Pharmacokinetic treatment profiles for a typical 65-kg adult.
Simulated whole-blood concentration-time profiles of chloroquine (n = 1,000), based on [119]. Solid black lines show the population mean concentration-time profiles, and the shaded areas show the 95% prediction intervals. The red dashed line indicates a putative EC50 value for SARS-CoV-2, scaled to total blood concentrations (chloroquine: 3.39 μM; hydroxychloroquine: 2.88 μM, using reported in vitro EC50 values [29, 54] and a blood-plasma ratio of 3:1 for chloroquine [13, 118] and 4:1 for hydroxychloroquine [38]). These are of uncertain relevance to antiviral activity in-vivo.
Fig 5
Fig 5. Pharmacokinetic prophylactic profiles of chloroquine and hydroxychloroquine.
Simulated whole-blood concentration-time profiles of chloroquine and hydroxychloroquine (n = 1,000 per body weight group), based on [119]. Solid black line shows the population mean concentration-time profile and the shaded area shows the 95% prediction interval. Red dashed line indicates a putative EC50 value for SARS-CoV-2 as in Fig 4. These EC50 estimates derived from in-vitro studies are of uncertain relevance to antiviral activity in-vivo.
See this image and copyright information in PMC

References

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