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Background. Recent in vitro studies have shown fluoxetine inhibits the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pathogen and one clinical study reported fluoxetine exposure at a median dose of 20mg in patients with the SARS-Cov-2 coronavirus disease 2019 (COVID-19) had a significantly lower risk of intubation and death. The aim of this study is to conduct in silico population dosing simulations to quantify the percentage of patients achieving a trough level for the effective concentration resulting in 90% inhibition (EC90) of SARS-Cov-2 as reported in Calu-3 human lung cells. Methods. Population pharmacokinetic parameter estimates for a structural one-compartment model with first-order absorption was used to simulate fluoxetine concentration-time data. A population of 1,000 individuals were simulated at standard fluoxetine doses (20mg/day, 40mg/day, and 60mg/day) to estimate the percentage of the patients achieving a trough level for the EC90 SARS-Cov-2 inhibitory concentration at each day throughout a 10-day treatment period. All analyses were conducted via statistical programming in R. Results. Standard fluoxetine antidepressant doses resulted in a range of 79% to 97% of the patient population achieving a trough target plasma concentration of 25.1 ng/ml which translates to lung-tissue distribution coefficient of 60-times higher (EC90 of 4.02 M). At a dose of 40mg per day, at least 85% of patients will reach the trough target EC90 concentration within 3-days. The findings of this pharmacokinetic dosing study corroborate both in vitro and observational clinical study findings showing fluoxetine inhibits the SARS-Cov-2 pathogen at commonly treated doses in the practice of psychiatry.
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10.1101/2020.12.17.20248442
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document_parses/pdf_json/4fc6cfde7285e834097064bb5315901d14ca889a.json
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Fluoxetine pharmacokinetics and tissue distribution suggest a possible role in reducing SARS-CoV-2 titers
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