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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 [IC50], 10.42 μM) and hypnozoites (IC50, 29.24 μM) in primary macaque hepatocytes when administered as a 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 7 consecutive days were evaluated for prophylaxis or radical cure of P. 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 7 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.

Original publication

DOI

10.1128/aac.00741-20

Type

Journal

Antimicrobial agents and chemotherapy

Publication Date

08/2020

Volume

64

Pages

e00741 - e00720

Addresses

Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

Keywords

Liver, Hepatocytes, Animals, Macaca mulatta, Plasmodium cynomolgi, Parasitemia, Malaria, Ivermectin, Chloroquine, Drug Combinations, Antimalarials, Drug Administration Schedule, Biological Availability, Drug Synergism, Female, Male, Schizonts, Primary Cell Culture