English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background.   Various  in vitro  studies have shown fluoxetine inhibits multiple variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen causing the coronavirus disease 2019 (COVID-19) worldwide pandemic and multiple observational clinical studies have shown that patients receiving fluoxetine experienced clinical benefit by lowering the risk of intubation and death. The aim of this study is to conduct population pharmacokinetic dosing simulations to quantify the percentage of patients achieving a  trough  level for the effective concentration resulting in 50% (EC50) and 90% (EC90) inhibition of SARS-CoV-2 as reported in Calu-3 human lung cells.    Methods.   Pharmacometric parameter estimates used in this study were obtained from the U.S. FDA website from a new drug application for fluoxetine hydrochloride. A population of 1,000 individuals were simulated at standard fluoxetine antidepressant doses (20 mg/day, 30 mg/day, 40 mg/day, 50 mg/day, and 60 mg/day) to estimate the percentage of the patients achieving a  trough  plasma level for the EC50 and EC90 SARS-CoV-2 inhibition. All analyses and graphing were conducted in R.    Results.   By day-10 at 20 mg/day 93.2% and 47% of the population will achieve the  trough  target plasma EC50 and EC90 concentrations, respectively, which translates to a lung tissue distribution coefficient of 60-times higher EC50 (283.6 ng/ml [0.82 mM]) and EC90 (1390.1 ng/ml [4.02 mM]). Further, by day-10 at an ideal dose of 40 mg/day, 99% and 93% of patients will reach the  trough  EC50 and EC90 concentrations, respectfully. Lastly, only a dose of 60 mg/day will reach the SARS-CoV-2 EC90 inhibitory concentration in the brain.    Conclusion.  Overall, with a minimum treatment period of 10-days and a minimum dose of 20 mg/day, this study corroborates  in vitro  studies reporting fluoxetine inhibiting SARS-CoV-2 titers and also multiple  observational  clinical studies showing therapeutic benefit of fluoxetine in COVID-19 patients.

Fluoxetine pharmacokinetics and tissue distribution quantitatively supports a therapeutic role in COVID-19 at a minimum dose of 20 mg per day