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.

中文翻译：

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大剂量伊维菌素和氯喹对恒河猴的安全性，药代动力学和肝阶段食蟹猕猴的影响

以前，伊维菌素（1-10 mg / kg）在口服给药的小鼠中可抑制伯氏疟原虫的肝阶段发育。在这里，伊维菌素在预防性高剂量给药时表现出对原猕猴肝细胞中的食蟹猴疟原虫（IC ₅₀ = 10.42μM）和次生子（IC ₅₀ = 29.24μM）体外发育的抑制作用，但在以自由基治疗方式给药时则没有抑制作用。评估连续7天服用和不服用氯喹（10 mg / kg）的口服伊维菌素（0.3、0.6和1.2 mg / kg）的安全性，药代动力学和疗效，用于预防或彻底治愈食蟹猴恒河猴的肝脏阶段。在任何伊维菌素剂量（0.3、0.6和1.2 mg / kg）下均未观察到对食蟹猕猴寄生虫的抑制或延迟。伊维菌素（0.6和1.2 mg / kg）和氯喹（10 mg / kg）的组合耐受性良好，没有不良事件，也没有观察到明显的药代动力学药物相互作用。伊维菌素每天重复给药7天不会抑制伊维菌素的生物利用度。最近证明，伊维菌素和氯喹都在体外抑制新型严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）的复制。有必要进一步在人体中进行伊维菌素和氯喹的临床试验，以评估它们在间日疟原虫中的作用 控制和辅助治疗COVID-19感染。