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• Rev. Soc. Bras. Med. Trop. 2 (5) • Oct 1968 • https://doi.org/10.1590/S0037-86821968000500002   copy

Experimental chemotherapy of Schistosomiasis III: laboratory and clinical trials with trichlorphone, an organophosphorus compound

Abstracts

Oogram studies have been carried out on mice, hamsters, and Cebus morikeys experimentally infected with Schistosoma mansoni and treated with trichlorphone (0,0-dimethyl 1-hydroxy-2, 2, 2-trichloroethylphosphonate). In mice, despite a slight hepatic shift of schistosomes, all animais presented oogram changes when dosed, per os, at the schedules of 200, and 100 mg/kg/day × 7. In hamsters, antischistosomal activity could be detected only at toxic leveis. In monkeys, trichlorphone showed insignificant action even after oral administration of 30 mg/kg/day for 10 consecutive days. In 5 volunteers, a sharp drop in cholinesterase plasma level was observed 24 hours after a single oral dose of 7.5 mg/kg. However, cholinesterase levels returned to the initial values within a period of 11 to 27 days. Trichlorphone was then administered to 12 schistosome patients (7.5 mg/kg/day, every fort- night, × 5). One month after therapy, interruption of egg laying was observed in 6 patients. Late parasitological control showed that all treated patients continued to pass viable S. mansoni eggs with their stools.

Ensaios pré-clinicos foram realizados em camundongos, hamsters e macacos Cebus experimentalmente infectados com Schistosoma mansoni e tratados com trichlorphone (0-0-dimetil 1-hidroxi-2, 2, 2-tricloroetilfosfonato). Em camundongos, apesar de ter sido discreto o deslocamento dos vermes para o fígado, em todos os animais houve alterações do oograma, quando foram administrados 200 e 100 mg/kg/dia × 7, per os. Em hamsters, a atividade sôbre os esquistossomos, só pôde ser detectada com doses tóxicas. Em macacos, o trichlorphone mostrou ação insignificante, mesmo após administração oral de 30 mg /kg/ dia durante 10 dias consecutivos. Em 5 voluntários, uma acentudada baixa da colinesterase plasmática, foi observada 24 horas após uma única dose oral de 7,5 mg/kg. Todavia, o nível da colinesterase voltou aos valores iniciais no período de 11 a 27 dias. O trichlorphone foi administrado a 12 pacientes com esquistossomose mansoni (7.5 mg/kg/dia, quinzenalmente, × 5). Um mês após o fim do tratamento, a interrupção da postura dos vermes foi observada em 6 pacientes. O controle parasitológico tardio revelou a ineficácia do tratamento em todos os pacientes.

Experimental chemotherapy of Schistosomiasis III. Laboratory and clinical trials with trichlorphone, an organophosphorus compound

Naftale KatzI; J. Pellegrino; J. Pedro Pereira

Address: Instituto Nacional de Endemias Rurais, C. Postal 1743, Belo Horizonte, Brazil

ABSTRACT

Oogram studies have been carried out on mice, hamsters, and Cebus morikeys experimentally infected with Schistosoma mansoni and treated with trichlorphone (0,0-dimethyl 1-hydroxy-2, 2, 2-trichloroethylphosphonate). In mice, despite a slight hepatic shift of schistosomes, all animais presented oogram changes when dosed, per os, at the schedules of 200, and 100 mg/kg/day × 7. In hamsters, antischistosomal activity could be detected only at toxic leveis. In monkeys, trichlorphone showed insignificant action even after oral administration of 30 mg/kg/day for 10 consecutive days.

In 5 volunteers, a sharp drop in cholinesterase plasma level was observed 24 hours after a single oral dose of 7.5 mg/kg. However, cholinesterase levels returned to the initial values within a period of 11 to 27 days. Trichlorphone was then administered to 12 schistosome patients (7.5 mg/kg/day, every fort- night, × 5). One month after therapy, interruption of egg laying was observed in 6 patients. Late parasitological control showed that all treated patients continued to pass viable S. mansoni eggs with their stools.

RESUMO

Ensaios pré-clinicos foram realizados em camundongos, hamsters e macacos Cebus experimentalmente infectados com Schistosoma mansoni e tratados com trichlorphone (0-0-dimetil 1-hidroxi-2, 2, 2-tricloroetilfosfonato). Em camundongos, apesar de ter sido discreto o deslocamento dos vermes para o fígado, em todos os animais houve alterações do oograma, quando foram administrados 200 e 100 mg/kg/dia × 7, per os. Em hamsters, a atividade sôbre os esquistossomos, só pôde ser detectada com doses tóxicas. Em macacos, o trichlorphone mostrou ação insignificante, mesmo após administração oral de 30 mg /kg/ dia durante 10 dias consecutivos.

Em 5 voluntários, uma acentudada baixa da colinesterase plasmática, foi observada 24 horas após uma única dose oral de 7,5 mg/kg. Todavia, o nível da colinesterase voltou aos valores iniciais no período de 11 a 27 dias. O trichlorphone foi administrado a 12 pacientes com esquistossomose mansoni (7.5 mg/kg/dia, quinzenalmente, × 5). Um mês após o fim do tratamento, a interrupção da postura dos vermes foi observada em 6 pacientes. O controle parasitológico tardio revelou a ineficácia do tratamento em todos os pacientes.

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Instituto Nacional de Endemias Rurais and Instituto de Biologia, Universidade Federal de Minas Gerais, Belo Horizonte, Rrazil. This study has been supported, in part, by research grants trom file U.S. Public Health Service (AI-05917-05), NIH, Bethesda, Maryland, and WHO, Geneva, Switzerland.

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Publication Dates

  • Publication in this collection
    06 Aug 2013
  • Date of issue
    Oct 1968
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