Severe Embryotoxicity of Artemisinin Derivatives in Experimental Animals, but Possibly Safe in Pregnant Women

摘要: Preclinical studies in rodents have demonstrated that artemisinins, especially injectable artesunate, can induce fetal death and congenital malformations at a low dose range. The embryotoxicity be induced those animals only within narrow window early embryogenesis. Evidence was presented the mechanism by which of artemisinins occurs seems to limited erythropoiesis vasculogenesis/ angiogenesis on very earliest developing red blood cells, causing severe anemia embryos with higher drug peak concentrations. However, this has not been convincingly observed clinical trials from 1,837 pregnant women, including 176 patients first trimester exposed an artemisinin agent or artemisinin-based combination therapy (ACT) 1989 2009. In rodent, sensitive cells are produced synchronously over one day single multiple exposures result high proportion cell deaths. contrast, primates required longer period treatment 12 days such embryonic loss. humans information is available about stage development; however, it known take place time period, may well 2 3 for malaria would produce serious toxic effects. addition, current oral intake, most commonly used route administration women ACT, results lower concentration shorter exposure concentration-course profile unlikely embryotoxicity. When relating animal human toxicity different pharmacokinetic profiles as reviewed present report provide great margin safety women.