S Xiao1, J You, J Mei, Y Hu, D Zhou, B A Catto. 1. Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, WHO Collaborating Center for Malaria, Schistosomiasis and Filariasis, Shanghai 200025, China.
Abstract
AIM: To compare the antischistosomal effect of racemic praziquantel (Pra) and its enantiomers, levopraziquantel (L-Pra) and dextropraziquantel (D-Pra), on different developmental stages of Schistosoma japonicum. METHODS: The in vitro effects of the drugs were determined in different stages of schistosomes maintained in RPMI 1640 supplemented with 20% calf serum. In vivo study mice infected with schistosome cercariae were treated intragastrically (ig) with Pra, L-Pra or D-Pra at different intervals after infection. The efficacy of the drugs was evaluated by residual mean worm number. RESULTS: Based on the degree of tegument damage induced by L-Pra, d28 and d35 schistosomes were most susceptible to L-Pra, while d14 schistosomules being least susceptible. At comparable concentrations of 0.1-1 g/ml, L-Pra was more active than Pra even when the concentration of L-Pra was reduced to one-half of the minimum effective concentration of Pra. At above-mentioned concentrations D-Pra exhibited no apparent in vitro effect on different stages of schistosomes. When infected mice were treated ig with L-Pra, Pra or D-Pra at a single dose of 300 mg/kg or 500 mg/kg, only the former two drugs showed apparent effect on d0, d21, d28 and d35 schistosomes and less or much less effect on d3, d7 and d14 schistosomules. D-Pra only exhibited a negligible effect on d35 adult schistosomes as compared with L-Pra and Pra. When mice infected with d35 adult schistosmes were treated ig with L-Pra 150 mg/kg, the efficacy was similar to that of mice treated with Pra 300 mg/kg. CONCLUSION: L-Pra is the principal active component against schistosomes in racemic Pra.
AIM: To compare the antischistosomal effect of racemic praziquantel (Pra) and its enantiomers, levopraziquantel (L-Pra) and dextropraziquantel (D-Pra), on different developmental stages of Schistosoma japonicum. METHODS: The in vitro effects of the drugs were determined in different stages of schistosomes maintained in RPMI 1640 supplemented with 20% calf serum. In vivo study mice infected with schistosome cercariae were treated intragastrically (ig) with Pra, L-Pra or D-Pra at different intervals after infection. The efficacy of the drugs was evaluated by residual mean worm number. RESULTS: Based on the degree of tegument damage induced by L-Pra, d28 and d35 schistosomes were most susceptible to L-Pra, while d14 schistosomules being least susceptible. At comparable concentrations of 0.1-1 g/ml, L-Pra was more active than Pra even when the concentration of L-Pra was reduced to one-half of the minimum effective concentration of Pra. At above-mentioned concentrations D-Pra exhibited no apparent in vitro effect on different stages of schistosomes. When infected mice were treated ig with L-Pra, Pra or D-Pra at a single dose of 300 mg/kg or 500 mg/kg, only the former two drugs showed apparent effect on d0, d21, d28 and d35 schistosomes and less or much less effect on d3, d7 and d14 schistosomules. D-Pra only exhibited a negligible effect on d35 adult schistosomes as compared with L-Pra and Pra. When mice infected with d35 adult schistosmes were treated ig with L-Pra 150 mg/kg, the efficacy was similar to that of mice treated with Pra 300 mg/kg. CONCLUSION: L-Pra is the principal active component against schistosomes in racemic Pra.