[Contragestational effects of dihydroartemisinin and artesunate].
In experiments carried out in mice, hamsters, guinea pigs and rabbits both dihydroartemisinin and artesunate showed contragestational effect. In mice and rabbits they caused embryo absorption whereas in hamsters and guinea pigs they induced abortion. The contragestational ED50 of dihydroartemisinin given sc on d 7 of pregnancy in mice and d 5 of pregnancy in hamsters were 32.8(27.7-38.9) mg.kg-1 and 6.1(5.6-6.7) mg.kg-1 respectively. The ED50 of this drug given im on d 18 of pregnancy in guinea pigs was 18.3(13.9-24.2) mg.kg-1. Dihydroartemisinin also showed mid-pregnancy terminating effect in hamsters. The contragestational ED50 of artesunate given sc on d 5 of pregnancy in hamsters and the ED50 of sodium artesunate given sc on d 5-8 of pregnancy in hamsters were 12.2(10.3-14.4) mg.kg-1 and 1.0(0.9-1.2) mg.kg-1 daily respectively. Results of light microscopic examination revealed that dihydroartemisinin was selectively toxic to embryo sac. At dose levels sufficient to induce embryo sac necrosis, dihydroartemisinin did not injure the uterus and ovary of the maternal animals. On the ground of the foregoing observations we consider that dihydroartemisinin, artesunate and their analogous drugs should not be used to treat malaria in pregnant women and there is the possibility to exploit intentional abortion agents from artemisinin derivatives.
Xu
J H
JH
Department of Pharmacology, Zhejiang Medical University, Hangzhou.
Zhang
Y P
YP
D000020:Abortifacient Agents, Nonsteroidal / Q000633:toxicity; D000818:Animals; D037621:Artemisinins; D000077332:Artesunate; D003271:Contraceptive Agents, Female / Q000633:toxicity; D006224:Cricetinae; D020964:Embryo Loss / Q000139:chemically induced; D005260:Female; D006168:Guinea Pigs; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011817:Rabbits; D012717:Sesquiterpenes / Q000633:toxicity; D014599:Uterus / Q000187:drug effects
D000020:Abortifacient Agents, Nonsteroidal; D037621:Artemisinins; D003271:Contraceptive Agents, Female; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol