RT Journal Article
SR Electronic
T1 Safety, pharmacokinetics, and liver-stage <em>Plasmodium cynomolgi</em> effect of high-dose ivermectin and chloroquine in Rhesus Macaques
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.27.065409
DO 10.1101/2020.04.27.065409
A1 Pattaraporn Vanachayangkul
A1 Rawiwan Im-erbsin
A1 Anchalee Tungtaeng
A1 Chanikarn Kodchakorn
A1 Alison Roth
A1 John Adams
A1 Chaiyaporn Chaisatit
A1 Piyaporn Saingam
A1 Richard J. Sciotti
A1 Gregory A. Reichard
A1 Christina K. Nolan
A1 Brandon S. Pybus
A1 Chad C. Black
A1 Luis A. Lugo
A1 Matthew D. Wegner
A1 Philip L. Smith
A1 Mariusz Wojnarski
A1 Brian A. Vesely
A1 Kevin C. Kobylinski
YR 2020
UL http://biorxiv.org/content/early/2020/04/29/2020.04.27.065409.abstract
AB Previously, ivermectin (1–10 mg/kg) was shown to inhibit liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure of Plasmodium cynomolgi liver-stages in Rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for seven days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in vitro. Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections.