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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Clin+Pharmacol+Ther 2020 ; 108 (4): 762-765 Nephropedia Template TP
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The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19 #MMPMID32378737
Schmith VD; Zhou JJ; Lohmer LRL
Clin Pharmacol Ther 2020[Oct]; 108 (4): 762-765 PMID32378737show ga
Caly et al.(1) reported that ivermectin inhibited severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in vitro for up to 48 hours using ivermectin at 5 muM. The concentration resulting in 50% inhibition (IC(50) ; 2 microM) was > 35x higher than the maximum plasma concentration (C(max) ) after oral administration of the approved dose of ivermectin when given fasted. Simulations were conducted using an available population pharmacokinetic model to predict total (bound and unbound) and unbound plasma concentration-time profiles after a single and repeat fasted administration of the approved dose of ivermectin (200 mug/kg), 60 mg, and 120 mg. Plasma total C(max) was determined and then multiplied by the lung:plasma ratio reported in cattle to predict the lung C(max) after administration of each single dose. Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC(50) , even for a dose level 10x higher than the approved dose. Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC(50) in the lungs after single oral administration of the approved dose (predicted lung: 0.0873 microM) or at doses 10x higher that the approved dose administered orally (predicted lung: 0.820 microM). In summary, the likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Repurposing drugs for use in coronavirus disease 2019 (COVID-19) treatment is an ideal strategy but is only feasible when product safety has been established and experiments of repurposed drugs are conducted at clinically relevant concentrations.