In vitro and in vivo studies of the effect of artemether on Schistosoma mansoni.

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RESUMO

To determine whether artemether, a derivative of the antimalarial agent qinghaosu, is therapeutically active against Schistosoma mansoni, we determined the in vitro, in vivo, and histopathologic effects of the drug on S. mansoni worms. In vitro, toxic effects of artemether on S. mansoni were not seen at concentrations of less than 100 micrograms/ml. However, in vivo, 30 and 50% reductions in the lengths of male and female worms, respectively, were observed 14 days after treatment. By 56 days worm dimensions had returned to control values. Similar reversible effects on male testes and female ovaries were seen. In vivo, a single oral dose of artemether (300 mg/kg) induced a shift of worms towards the liver within 8 h after treatment. By 3 and 14 days after treatment, 99 and 76%, respectively, of worms were still in the liver. In vivo, the therapeutic effect of artemether on adult S. mansoni treated on day 56 after infection was modest. Doses as high as 1,200 mg (200 mg/kg per day, six doses) resulted in a worm reduction rate of only 39%. However, in infected mice treated on day 14 or 21 after infection, worm reduction rates of 83 to 98% were obtained. Thus, artemether exhibited modest in vitro and in vivo activities against adult S. mansoni but was twofold more active against 2- to 3-week-old liver-stage parasites.

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