Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum
The increasing resistance of P. falciparum strains to the current antimalarial drugs makes the searching of new drugs an urgent task. The compound Ro 42-1611 is an antimalarial drug that arises from a chinese herb Artabotrys uncinatus. Since its synthesis, Ro 42-1611 was used in three different c...
| Autor principal: | SILVA, Rita do Socorro Uchôa |
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| Grau: | Dissertação |
| Idioma: | por |
| Publicado em: |
Universidade Federal do Pará
2013
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| Acesso em linha: |
http://repositorio.ufpa.br/jspui/handle/2011/3565 |
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ir-2011-3565 |
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ir-2011-35652019-05-21T15:31:25Z Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum SILVA, Rita do Socorro Uchôa SOUZA, José Maria de http://lattes.cnpq.br/6459204248879587 Malária falciparum Plasmodium falciparum Antimaláricos Ro42-1611 Terapêutica Marabá - PA Pará - Estado Amazônia brasileira CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS The increasing resistance of P. falciparum strains to the current antimalarial drugs makes the searching of new drugs an urgent task. The compound Ro 42-1611 is an antimalarial drug that arises from a chinese herb Artabotrys uncinatus. Since its synthesis, Ro 42-1611 was used in three different clinical trials to treat falciparum malaria in Africa, but how it works in the South America malaria patients is obscure. Althouh being an effective antimalarial, a proper therapeutic dose to achieve the supressive cure of falciparum malaria has not been established yet. The purpose of this study is to evaluate the tolerance, the toxicity and the efficacy of 3 different dose schedules of Ro 42-1611 in the treatment of falciparum malaria. It was an open, prospective and randomized trial carried out in Maraba/Para State in male patients with maximum 80 kg bodyweight. All patients had fever or another constitutional malaria symptom and had a positive thick blood smear to P. falciparum (≥ 200 and ≤ 50,000 parasites/mm³). In a hospital, they were assigned into 3 groups according to drug administration time: Group I - 1,500 mg twice a day for 24 hours; Group II - 1,500 mg twice a day for 48 hours and Group III - 1,500 mg twice a day for 72 hours. Before treatment, the following procedures were recorded from all patients: personal data, height and weight, malarial signs and symptoms, history of simultaneous drug intake, body temperature, vital functions (respiratory rate, blood pressure), parasite count, haematology and blood chemistry assesments and electrocardiogram. Ouring the treatment, all those parameters were followed, including adverse reactions to Ro 42-1611. Statistical analysis (Friedman variance test) were performed on laboratory tests results. Sixteen patients were enrolled in the study: 5 patients in Group I; 6 in Group II and 5 patients in Group III. Among patients, age ranged from 17 to 41 years old (mean 266). body weight from 44 to 72 kg (mean 54.9). The assexual parasite count ranged from 200 to 40,000 parasites/mm³ . Regarding those variables, there were homogeneity in 3 groups. According to the protocol, clinical and laboratory data were evaluated, with the following results: the minimum and the maximum fever clearence time was 9 to 48 hours respectively. The mean assexual parasite clearence was 53.6 hours, without any statistical significance among the groups (p=0.7264). There were statistical significative difference (p=0.0046) in the hematocrit values before treatment (00), and the third (02) and the eighth (07) day of the follow-up. It was observed an increase in the leukocyte count between 02 and 07, also of statistical significance (p=0.0171), as well in the platelets of 00 and 07/02 and 07 (p=0.0001). Between DO and 07, statistical significative reduction ocurred in the values of total bilirrubin (p=0.0024), alkaline phosphatase (p=0.0195) and urea (p=0.0168). There were no statistical significative difference nor in the evalution of electrocardiogram results neither in the blood pressure. Short adverse reactions were mild to moderate. In the end of the treatment, 87,5% of patients were completely free of parasites, but just 2 achieved a radical cure (12,5%), both included in Group III. Any of the schedule treatment showed efficacy. Perhaps such efficacy might be attained using Ro 42-1611 in a superior dose, for a longer period of time or in association with other antimalarial in further studies. FUNASA/PA - Fundação Nacional de Saúde A resistência crescente do P. falciparum aos antimaláricos habitualmente empregados, torna urgente a avaliação de novas drogas. O Ro 42-1611 é um antimalárico derivado da planta chinesa Arlabotrys uncinatus. Usado apenas na África em três trabalhos no tratamento da malária por P. falciparum, tem sua ação desconhecida em sul-americanos com esta doença. Apesar do efeito antimalárico ter sido comprovado, ainda não se encontrou a dose adequada para o tratamento supressivo do P. falciparum. Avaliar a tolerância, a toxicidade e a eficácia de três diferentes doses do Ro 42-1611 no tratamento da malária por P. falciparum é o que objetiva este trabalho. O estudo foi realizado em Marabá-Pará, caracterizando-se por ser aberto, prospectivo e randomizado; incluiu pacientes voluntário s, adultos, masculinos, de peso corporal até 80 kg; febris ou com outros sintomas constitucionais de malária e com gota espessa positiva para P. falciparum ( ≥ 200 e ≤ 50.000 parasitas/mm³ de sangue). Grupos de estudo: I -1.500 mg de 12/12 horas por 1 dia; II -1.500 mg de 12/12 horas por2 dias e III -1.500 mg de 12/12 horas por 3 dias. Todos os pacientes foram tratados em regime hospitalar, sendo avaliados no pré-tratamento através de: dados pessoais e biométricos, sinais e sintomas, uso de medicação concomitante, temperatura axilar, freqüência respiratória, pressão arterial, eletrocardiograma, parasitemia, exames hematológicos e bioquímicos. A partir do início da terapêutica, a avaliação destes parâmetros foi feita seguindo protocolo próprio, incluindo a anotação de efeitos colaterais. A análise de variância de Friedman foi usada para avaliar os valores obtidos nos exames hematológicos e bioquímicos. Foram selecionados 16 pacientes, sendo 5 alocados no grupo I, 6 no II e 5 no III. Idade variou de 17 a 41 anos (média: 26,6), peso corporal de 44 a 72 kg (média: 54,9), parasitemia assexuada inicial de 200 a 40.000 formas/mm³ de sangue, sendo os grupos homogêneos quanto a estas variáveis. A febre desapareceu no mínimo com 9 e no máximo com 48 horas a partir do início da terapêutica. A avaliação do traçado eletrocardiográfico e da pressão arterial não mostrou alterações significativas. O desaparecimento da parasitemia assexuada ocorreu em média com 53,6 horas, não se evidenciando diferenças estatísticas i significantes entre os grupos (p=0,7264). Houve uma diminuição significativa entre o pré-tratamento (D0) e o terceiro (D2) e oitavo (D7) dias de acompanhamento quanto os níveis de hematócrito (p=0,0046), um aumento no número de leucócitos entre D2 e D7 (p=0,0171) e plaquetas entre D0 e D7, assim como entre D2 e D7 (p< 0,0001). Entre D0 e D7 detectou-se diminuição nos níveis de bilirrubina total (p=0,0024), fosfatase alcalina (p=0,0195) e uréia (p=0,0168). Efeitos colaterais foram em geral leves ou moderados e de curta duração. Do total de pacientes, 87,5% obtiveram desaparecimento da parasitemia assexuada, porém apenas 2 (12,5%) curaram, ambos incluídos no grupo III. Nenhum dos esquemas posológicos usados foi adequado para a cura desta doença. Talvez em estudos posteriores usando a droga em maior dose ou por maior número de dias ou ainda associando-a a outros antimaláricos, possa obter-se eficácia adequada. 2013-03-18T13:42:37Z 2013-03-18T13:42:37Z 1997-12-04 Dissertação SILVA, Rita do Socorro Uchôa. Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum. 1997. 117 f. Dissertação (Mestrado) - Universidade Federal do Pará, Núcleo de Medicina Tropical, Instituto Evandro Chagas, Belém, 1997. Curso de Pós-Graduação em Medicina Tropical. http://repositorio.ufpa.br/jspui/handle/2011/3565 por Acesso Aberto application/pdf Universidade Federal do Pará Instituto Evandro Chagas Brasil Núcleo de Medicina Tropical UFPA IEC Programa de Pós-Graduação em Doenças Tropicais |
| institution |
Repositório Institucional - Universidade Federal do Pará |
| collection |
RI-UFPA |
| language |
por |
| topic |
Malária falciparum Plasmodium falciparum Antimaláricos Ro42-1611 Terapêutica Marabá - PA Pará - Estado Amazônia brasileira CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS |
| spellingShingle |
Malária falciparum Plasmodium falciparum Antimaláricos Ro42-1611 Terapêutica Marabá - PA Pará - Estado Amazônia brasileira CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS SILVA, Rita do Socorro Uchôa Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| topic_facet |
Malária falciparum Plasmodium falciparum Antimaláricos Ro42-1611 Terapêutica Marabá - PA Pará - Estado Amazônia brasileira CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS |
| description |
The increasing resistance of P. falciparum strains to the current antimalarial drugs
makes the searching of new drugs an urgent task. The compound Ro 42-1611 is an
antimalarial drug that arises from a chinese herb Artabotrys uncinatus. Since its
synthesis, Ro 42-1611 was used in three different clinical trials to treat falciparum
malaria in Africa, but how it works in the South America malaria patients is obscure.
Althouh being an effective antimalarial, a proper therapeutic dose to achieve the
supressive cure of falciparum malaria has not been established yet. The purpose of
this study is to evaluate the tolerance, the toxicity and the efficacy of 3 different dose
schedules of Ro 42-1611 in the treatment of falciparum malaria. It was an open,
prospective and randomized trial carried out in Maraba/Para State in male patients
with maximum 80 kg bodyweight. All patients had fever or another constitutional
malaria symptom and had a positive thick blood smear to P. falciparum (≥ 200 and ≤
50,000 parasites/mm³). In a hospital, they were assigned into 3 groups according to
drug administration time: Group I - 1,500 mg twice a day for 24 hours; Group II -
1,500 mg twice a day for 48 hours and Group III - 1,500 mg twice a day for 72 hours.
Before treatment, the following procedures were recorded from all patients: personal
data, height and weight, malarial signs and symptoms, history of simultaneous drug
intake, body temperature, vital functions (respiratory rate, blood pressure), parasite
count, haematology and blood chemistry assesments and electrocardiogram. Ouring
the treatment, all those parameters were followed, including adverse reactions to Ro
42-1611. Statistical analysis (Friedman variance test) were performed on laboratory
tests results. Sixteen patients were enrolled in the study: 5 patients in Group I; 6 in
Group II and 5 patients in Group III. Among patients, age ranged from 17 to 41 years
old (mean 266). body weight from 44 to 72 kg (mean 54.9). The assexual parasite
count ranged from 200 to 40,000 parasites/mm³
. Regarding those variables, there
were homogeneity in 3 groups. According to the protocol, clinical and laboratory data
were evaluated, with the following results: the minimum and the maximum fever
clearence time was 9 to 48 hours respectively. The mean assexual parasite
clearence was 53.6 hours, without any statistical significance among the groups
(p=0.7264). There were statistical significative difference (p=0.0046) in the
hematocrit values before treatment (00), and the third (02) and the eighth (07) day
of the follow-up. It was observed an increase in the leukocyte count between 02 and
07, also of statistical significance (p=0.0171), as well in the platelets of 00 and
07/02 and 07 (p=0.0001). Between DO and 07, statistical significative reduction
ocurred in the values of total bilirrubin (p=0.0024), alkaline phosphatase (p=0.0195)
and urea (p=0.0168). There were no statistical significative difference nor in the
evalution of electrocardiogram results neither in the blood pressure. Short adverse
reactions were mild to moderate. In the end of the treatment, 87,5% of patients were
completely free of parasites, but just 2 achieved a radical cure (12,5%), both
included in Group III. Any of the schedule treatment showed efficacy. Perhaps such
efficacy might be attained using Ro 42-1611 in a superior dose, for a longer period
of time or in association with other antimalarial in further studies. |
| author_additional |
SOUZA, José Maria de |
| author_additionalStr |
SOUZA, José Maria de |
| format |
Dissertação |
| author |
SILVA, Rita do Socorro Uchôa |
| title |
Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| title_short |
Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| title_full |
Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| title_fullStr |
Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| title_full_unstemmed |
Estudo de dose adequada da droga RO42-1611 (Arteflene) no tratamento da malária por Plasmodium falciparum |
| title_sort |
estudo de dose adequada da droga ro42-1611 (arteflene) no tratamento da malária por plasmodium falciparum |
| publisher |
Universidade Federal do Pará |
| publishDate |
2013 |
| url |
http://repositorio.ufpa.br/jspui/handle/2011/3565 |
| _version_ |
1787148437287862272 |
| score |
11.653393 |