Evaluation of the developmental toxicity of artemether during different phases of rat pregnancy

The present investigation was performed to examine the effect of artemether on rat pregnancy and embryonic/fetal development during different phases of pregnancy. Artemether was administered orally to Wistar rats at doses 3.5 and 7 mg/kg during blastogenesis, organogenesis and fetal period. When administered during blastogenesis, the preimplantation loss, number of implantations, resorptions, living fetuses, external and skeletal examination did not differ from those of control, however the higher dose induced reduction in fetal body weight and caused pre-term delivery in 3 of 10 pregnant rats. During organogenesis complete fetal resorption was observed in all dams treated with the higher dose, while in the lower dose 32% of implants were resorbed and live fetuses showed decreased fetal weight with low incidence of skeletal retardation. Artemether did not adversely affect prenatal development in rats treated during the fetal period although the higher dose level induced reduction in fetal body weight. In conclusion, no evidence of maternal toxicity, artemether was embryolethal at 3.5 and 7 mg/kg when dosed during organogenesis, the surviving fetuses showed fetal growth retardation without incidence of malformations, treatment during blastogenesis and fetal period had no lethal or teratogenic effect although the mean fetal body weight was significantly lower than control. (C) 2009 Elsevier Ltd. All rights reserved.