Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention

  1. Mohammad Tarek
  2. Andrea Savarino

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Abstract

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  1. Version published to 10.1007/s13318-020-00640-6
  2. ScreenIT

    SciScore for 10.1101/2020.04.23.20076471: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Mathematical modelling was implemented using Python programming language v 3.7 (http://www.python.org), ODEINT function of SciPy package was used for solving ordinary differential equations [10], numerical solutions were applied through NumPy package [11] and simulations were plotted within a 10 days’ time frame using Matplotlib package [12].
    Python
    suggested: (IPython, RRID:SCR_001658)
    SciPy
    suggested: (SciPy, RRID:SCR_008058)
    NumPy
    suggested: (NumPy, RRID:SCR_008633)
    Matplotlib
    suggested: (MatPlotLib, RRID:SCR_008624)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Both studies have their own limitations and very limited statistical power, due to the fact that they were prepared during an emergency. The discrepancy of the results obtained may reside, according to the results of the present study, in dosage of hydroxychloroquine adopted, with the French study reporting positive results using 600 mg/day of hydroxychloroquine and the Chinese study being unable to show any efficacy following adoption of a lower dosage (400 mg/day). Furthermore, the reported response to hydroxychloroquine in the French study is incomplete, and the authors had to add another experimental drug repositioned as an antiviral (azithromycin) in order to increase efficacy. These considerations are in line with the results obtained in randomized clinical trials using chloroquine and hydroxychloroquine at an equivalent dosage superior to that reported in the two aforementioned studies [20-22]. As the safety margin of chloroquine/hydroxychloroquine is narrow [23], administration of higher dosages is unfortunately hampered by toxicity, as shown by Borba et al. [22], although recent data show that the toxicity observed by Borba et al. could in fact be ascribed by the concomitant administration of azithromycin [24]. Our results agree in part with the simulations conducted by Arnold and Buckner [25], showing that only the 600 mg/day regimen might have a significant impact on viral replication according to all parameters that they adopted, and those of Garcia-Cremades et al...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.04.23.20076471v1 on medRxiv