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Safety, Pharmacokinetics, and Activity of High-Dose Ivermectin and Chloroquine against the Liver Stage of Plasmodium cynomolgi Infection in Rhesus Macaques. | LitMetric

AI Article Synopsis

  • * The safety and efficacy of different doses of oral ivermectin, with or without chloroquine, were tested in rhesus macaques for preventing or curing liver stages, but no significant impact on blood-stage parasite development was observed.
  • * Both ivermectin and chloroquine were well-tolerated in combinations, with no serious side effects or drug interactions noted, leading to a call for further human trials to explore their effectiveness against COVID-19.

Article Abstract

Previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of in orally dosed mice. Here, ivermectin showed inhibition of the development of schizonts (50% inhibitory concentration [IC], 10.42 μM) and hypnozoites (IC, 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 liver stages in rhesus macaques. No inhibition or delay to blood-stage 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) Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in control and as adjunctive therapies against COVID-19 infections.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449176PMC
http://dx.doi.org/10.1128/AAC.00741-20DOI Listing

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