Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus Macaques
Pattaraporn Vanachayangkul, Rawiwan Im‐Erbsin, Anchalee Tungtaeng, Chanikarn Kodchakorn, Alison Roth, John H. Adams, Chaiyaporn Chaisatit, Piyaporn Saingam, Richard J. Sciotti, Gregory A. Reichard, Christina K. Nolan, Brandon Pybus, Chad C. Black, Luis A. Lugo‐Roman, Matthew D. Wegner, Philip L. Smith, Mariusz Wojnarski, Brian A. Vesely, Kevin C. Kobylinski
Abstract
Previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (50% inhibitory concentration [IC 50 ], 10.42 μM) and hypnozoites (IC 50 , 29.24 μM) in primary macaque hepatocytes when administered as a high dose prophylactically but not when administered in radical cure mode.