However, there was a reduction in olfactory deficit (measured using a food-finding test) and a reduction in the interleukin (IL)-6:IL-10 ratio in lung tissues.
16-19 Subcutaneous administration of ivermectin 400 µg/kg had no effect on SARS-CoV-2 viral loads in hamsters. 14,15 Even though ivermectin appears to accumulate in the lung tissue, predicted systemic plasma and lung tissue concentrations are much lower than 2 µM, the half-maximal inhibitory concentration (IC 50) against SARS-CoV-2 in vitro. 13 However, pharmacokinetic and pharmacodynamic studies suggest that achieving the plasma concentrations necessary for the antiviral efficacy detected in vitro would require administration of doses up to 100-fold higher than those approved for use in humans. Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in cell cultures. Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin in the treatment of COVID-19.
4,7-9 Despite this in vitro activity, no clinical trials have reported a clinical benefit for ivermectin in patients with these viruses. 6 Ivermectin is thought to be a host-directed agent, which may be the basis for its broad-spectrum activity in vitro against the viruses that cause dengue, Zika, HIV, and yellow fever. 4,5 In addition, ivermectin docking may interfere with the attachment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human cell membrane. Reports from in vitro studies suggest that ivermectin acts by inhibiting the host importin alpha/beta-1 nuclear transport proteins, which are part of a key intracellular transport process that viruses hijack to enhance infection by suppressing the host’s antiviral response. Proposed Mechanism of Action and Rationale for Use in Patients With COVID-19 1,3 Ivermectin is not approved by the FDA for the treatment of any viral infection. 2 For these indications, ivermectin has been widely used and is generally well tolerated. 1 It is also being evaluated for its potential to reduce the rate of malaria transmission by killing mosquitoes that feed on treated humans and livestock. Ivermectin is a Food and Drug Administration (FDA)-approved antiparasitic drug that is used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies.
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