关键词: 青蒿素, 青蒿素哌喹复方, 大鼠, 发育毒性, 致畸

Abstract: BACKGROUND AND AIM: Artemisinin_piperaquine combination (ATQ) is comprised of artemisinin and piperaquine for the treatment of falciparum malaria. To test the developmental toxicity of the combination, embryo_fetal development studies were conducted in rats. MATERIALS AND METHODS: SD rats were divided into 6 groups (18 animals per group). On days 7－17 of gestation, ATQ in 4 doses of 35, 70, 120 and 200 mg/(kg·d) were orally administrated to 4 groups of rats, and a similar group was dosed with the vehicle and cyclophosphamide to serve as control. Body weight, food consumption and clinical observation data were collected during the study. On day 20 of gestation, all rats were sacrificed. RESULTS: Fetal developmental retardation was observed in groups of 70, 120 and 200 mg/(kg·d)doses. Groups of 120 and 200 mg/kg doses showed embryotoxicity, with fetal resorption of 23.5％ and 36.4％, respectively, and a low incidence of skeletal abnormalities with protruding, absent, incomplete ossification and short supernumerary ribs. No toxicity was observed in group of 35 mg/kg dose. CONCLUSION: ATQ had developmental toxicity and 35 mg/(kg·d)was the maximum safe dose in pregnant SD rats.

Key words: artemisinin, artemisinin_piperaquine combination, rats, developmental toxicity, teratogenicity