Sub-acute toxicological study of artemisinin-piperaquine tablets in rhesus monkeys.

Artemisinin-piperaquine tablet (trade name Artequick, ATQ), is a novel combination therapy for the treatment of malaria and especially for resistant P.falciparum malaria. The aim of our study was to assess the potential sub-acute toxicity profile of ATQ by oral administration route in rhesus monkeys. Monkeys were administrated once daily with doses of ATQ (39.1, 78.2, 156.4 mg/kg) for 21 days and then followed-up a 56-day recovery period. The administration of ATQ at high dose produced significant changes in the clinical signs primarily involved in gastrointestinal and nervous systems. Body weight loss, significant decrease in food consumption and body temperature were observed in monkeys at high dose. Various hematological and biochemical parameters changes, and significant pathological lesions (adrenal gland, thymus and femur epiphyseal) were observed in the middle and high dose group at the end of the treatment period. However, the toxic effects of ATQ were reversed and delayed adverse drug reaction did not occur during the recovery period. Based on the results of this study, the no-observed-adverse-effect level for ATQ was considered to be 39.1 mg/kg in rhesus monkeys.