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Abstract:
Praziquantel (2-cyclohexylcarbonyl-1,2,3,6,7, 11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one, EMBAY 8440, Biltricide) is an anthelminthic drug with activity against all species of schistosomes pathogenic to man and a wide range of cestodes, including the cysticerci of Taenia solium in human tissues and organs, also the CNS. Praziquantel does not reveal any undesired pharmacodynamic effects. After oral administration praziquantel is quantitatively and rapidly absorbed, metabolized and excreted as a variety of metabolites predominantly via the kidneys. The acute toxicity in rats, mice, rabbits and dogs is very low. Rats tolerated by oral administration doses of up to 1000 mg/kg repeated daily for four weeks, and dogs up to 180 mg/kg for 13 weeks without any organ damage. Praziquantel did not disturb reproduction in rats (up to F2-generation), nor did it reveal teratogenic effects in mice, rats and rabbits. In extensive mutagenicity trials performed by different laboratories worldwide, in a variety of test systems, no induction of point mutations, gene conversion, DNA-repair, sister chromatid exchanges (SCEs), or X-linked recessive lethals was detected. Besides, Salmonella tests with urines of praziquantel treated mice, rats, healthy and Schistosoma-infected persons gave no indication of a mutagenic effect. In different in vivo mammalian assays praziquantel not mutagenic either. Low toxicity of praziquantel was not mutagenic either. Low toxicity of praziquantel was demonstrated also in the combined chronic toxicity and carcinogenicity tests which were performed in rats and Syrian hamsters. In none of these species praziquantel exerted a carcinogenic action, and both doses were tolerated.