key: cord-0859260-jonqsh74
authors: Peña‐Silva, Ricardo; Duffull, Stephen B.; Steer, Andrew C.; Jaramillo‐Rincon, Sandra X.; Gwee, Amanda; Zhu, Xiao
title: Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID‐19
date: 2020-07-17
journal: Br J Clin Pharmacol
DOI: 10.1111/bcp.14476
sha: eae373c6f95bd4b3019d53c614272be6a19e4578
doc_id: 859260
cord_uid: jonqsh74

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broad anti-viral activity through inhibition of viral proteins including importin α/β1 heterodimer and integrase protein. 2 Caly and colleagues reported that the addition of ivermectin at a concentration of 5μM (twice the reported IC 50 ) to Vero-hSLAM cells, 2 h post infection with SARS-CoV-2, resulted in a reduction in the viral RNA load by 99.98% at 48 h. 1 The authors suggested that this drug could reduce the viral load in infected patients, with potential effect on disease progression and spread.

While the findings by Caly and colleagues provide some promise, several pharmacokinetic factors limit the immediate translation of their findings, and there is no evidence that the 5μM concentration of ivermectin used by Caly and colleagues in their in vitro SARS-CoV-2 experiment, can be achieved in vivo. First, the pharmacokinetics of ivermectin in humans is well described, [3] [4] [5] and even with the highest reported dose of approximately 1700 μg/kg (i.e., 8.5 times the FDAapproved dose of 200 μg/kg), the maximum plasma concentration was only 0.28μM. 5 Second, 93% of ivermectin is bound to plasma proteins that limit its cellular uptake by endothelial cells. 6 F I G U R E 1 Expected free plasma concentrations of ivermectin based on 93% binding to plasma proteins and previously published total plasma concentrations. [3] [4] [5] When necessary, an estimated body weight of 70 kg was used for calculations. Note that none of the doses reached the 5μM concentration required for the antiviral effect of ivermectin (dotted line)

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