Fluoxetine pharmacokinetics and tissue distribution suggest a possible role in reducing SARS-CoV-2 titers

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1. Version published to 10.12688/f1000research.53275.1

   Jun 16, 2021
2. 

   ScreenIT

   Dec 21, 2020

   SciScore for 10.1101/2020.12.17.20248442: (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

   Experimental Models: Cell Lines
   Sentences	Resources
   For all calculations, the trough target plasma concentration is referenced from the Schloer et al. study who reported after a 48-hour incubation period in Calu-3 lung cells the 90% maximal effective concentration is 4.02 μM (Schloer et al., 2020) which is significantly higher than the EC90 in Vero E6 cells (1.81 μM) and EC50 results from Zimniak et al. and the Schloer et al. studies (Schloer et al., 2020; Zimniak et al., 2020).	Vero E6 suggested: None
   Statistical results providing percentage estimates are calculated from trough concentrations of patients achieving the effective …

   SciScore for 10.1101/2020.12.17.20248442: (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

   Experimental Models: Cell Lines
   Sentences	Resources
   For all calculations, the trough target plasma concentration is referenced from the Schloer et al. study who reported after a 48-hour incubation period in Calu-3 lung cells the 90% maximal effective concentration is 4.02 μM (Schloer et al., 2020) which is significantly higher than the EC90 in Vero E6 cells (1.81 μM) and EC50 results from Zimniak et al. and the Schloer et al. studies (Schloer et al., 2020; Zimniak et al., 2020).	Vero E6 suggested: None
   Statistical results providing percentage estimates are calculated from trough concentrations of patients achieving the effective concentrations and is referenced from the Schloer et al. study reporting the EC90 value in human-lung Calu-3 cells.	Calu-3 suggested: KCLB Cat# 30055, RRID:CVCL_0609)

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   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).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   A limitation of this study is associated with the previously validated fluoxetine pharmacometric model being in women and did not include men (Tanoshima et al., 2014). However, as shown from the aforementioned FDA Adverse Events Reporting System data, women represented 58% of all ADR cases overall from the reporting period of 1982 to 2020. Overall, from a drug-safety perspective, prior to administering fluoxetine, a careful review of all patient medications and clinical status by clinical pharmacologist-physicians would be recommended to avoid drug interactions due to fluoxetine’s ability to strongly inhibit CYP2C19 and CYP2D6 (Hefner, 2018). Compounds that are sensitive and moderate CYP2C19 (e.g. omeprazole diazepam, lansoprazole, rabeprazole, voriconazole) and CYP2D6 substrates (e.g. dextromethorphan, eliglustat, nebivolol, tolterodine, encainide, metoprolol, propranolol, tramadol) will have an increase total area-under-the-concentration-time curve of ≥ 5-fold drug exposure when treated with fluoxetine (United States Food and Drug Administration, 2020). Lastly, patients who have a pharmacogenomic profile of being a CYP2D6 Poor Metabolizer or Intermediate Metabolizers should be closely monitored for potential fluoxetine side-effects, but may also have a higher rate of achieving the target trough EC90 concentration at a 20mg daily fluoxetine dose relative to CYP2D6 Normal (Extensive) Metabolizers.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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

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

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   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.

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3. 

   Version published to 10.1101/2020.12.17.20248442v1 on medRxiv

   Dec 19, 2020