Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view

Georgi Momekov; Denitsa Momekova

The COVID-19 pandemics has fuelled much research efforts towards repurposing of existing drugs as possible antiviral agents, whereby the therapeutic strategies have been largely based on preexisting data for the preceding coronaviral outbreaks TORS and MERS 1-3 . The drug regulatory agencies, health authorities, key opinion leaders and policy decision makers have been significantly strained by the dilemma of evidence-based medicine and good clinical practice versus the prompt need for safe and effective treatment 4 . Unfortunately we have been witnessing huge public and political pressure for legitimation of drug-repurposing and off-label use worldwide, which nonetheless could be regarded as an acceptable compromise, pending the emergency of the current situation, but only in case of drugs with well-defined safety profiles and at least some clinical evidence in COVID-19 4, 5 . Conversely most of the treatment protocols are based on observational studies and anecdotic reports 4,6-9 , albeit with a hope that the promptly emerging data from randomized studies will enable switching COVID-19 treatment back to the avenues of evidence-based medicine 10 . An exceptionally alarming phenomenon however is the public communication of drugs with preliminary in vitro activities against SARS-CoV-2 as potential therapeutics for COVID-19 eventually causing malignant reverberation in social media. Such example is the otherwise very interesting study of Caly et al., recently published in Antiviral Research 11 . This paper is describing the in vitro antiviral activity of the antiparasitic agent ivermectin in a model of Vero/hSLAM cells infected with a SARS-CoV-2 isolate (Australia/VIC01/2020) 11 . The authors have performed a pilot experiment using continuous exposure of the cells to ivermectin at 5 µmol/L and found time-dependent decrease of cell associated and supernatant viral RNA. Thereafter the antiviral activity was assessed following continuous exposure to serial dilutions of ivermectin, which caused concentration-dependent antiviral effects with practically total eradication at 5 µmol/L and halfmaximal inhibition at approximately 2.5 µmol/L 11 .