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https://www.arca.fiocruz.br/handle/icict/32587
SAFETY, EFFICACY AND PHARMACOKINETIC EVALUATIONS OF A NEW COATED CHLOROQUINE TABLET IN A SINGLE-ARM OPEN-LABEL NON-COMPARATIVE TRIAL IN BRAZIL: A STEP TOWARDS A USER-FRIENDLY MALARIA VIVAX TREATMENT
Plasmodium vivax,
Antimalarial treatment
Chloroquine
Pharmacokinetics
Adherence
Clinical trial
Autor(es)
Afiliação
Tropical Medicine Research Center of Rondônia. Porto Velho, RO, Brazil / Fundação Oswaldo Cruz. Instituto Nacional Institute de Infectologia Evandro Chagas. Laboratório de Parasitologia. Rio de Janeiro, RJ, Brasil / Federal University of Rondônia. Porto Velho, RO, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Rio de Janeiro, RJ, Brasil / Liverpool School of Tropical Medicine. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Nacional Institute de Infectologia Evandro Chagas. Laboratório de Parasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Desenvolvimento de Tecnologia em Saúde. Serviço de Equivalência Farmacêutica e Farmacocinética. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.
Tropical Medicine Research Center of Rondônia. Porto Velho, RO, Brazil.
Ministry of Health. National Programme of Malaria Control. Brasília, DF, Brazil.
Federal University of Mato Grosso. Julio Müller Hospital. Cuiabá, MT, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Rio de Janeiro, RJ, Brasil / Liverpool School of Tropical Medicine. Liverpool, UK.
Fundação Oswaldo Cruz. Instituto Nacional Institute de Infectologia Evandro Chagas. Laboratório de Parasitologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Vice-Presidência de Pesquisa e Laboratórios de Referência. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Desenvolvimento de Tecnologia em Saúde. Serviço de Equivalência Farmacêutica e Farmacocinética. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.
Tropical Medicine Research Center of Rondônia. Porto Velho, RO, Brazil.
Ministry of Health. National Programme of Malaria Control. Brasília, DF, Brazil.
Federal University of Mato Grosso. Julio Müller Hospital. Cuiabá, MT, Brazil.
Resumo em Inglês
Background: Malaria remains a major public health problem, with half the world population at risk of contracting
malaria. The effects of Plasmodium vivax on prosperity and longevity have been highlighted in several recent clinical case reports. The first line of vivax treatment drugs has seen no radical innovation for more than 60 years. This study introduces a subtle incremental innovation to vivax treatment: a chloroquine and primaquine co-blister. The co-blister includes a new chloroquine formulation incorporating coated tablets to mask the drug’s bitter taste and user-friendly packaging containing tablets of each drug, which may improve patient adherence and facilitate the appropriate use of the drugs. This new formulation will replace the non-coated chloroquine distributed in Brazil. Methods: Patients were orally treated with 150 mg coated chloroquine tablets for 3 days: an initial 450 mg dose, followed by two 300 mg doses. The patients were treated concomitantly with two 15 mg primaquine tablets for 7–9 days, according to their weight. The primary objective of this study was to prove parasitological and clinical cure rates above 90 % by day 28. Results: This single-arm open-label non-comparative trial was conducted according to the WHO recommended methodology for the surveillance of anti-malarial drug efficacy in the Brazilian Amazon. On day 28, the parasitological and clinical response was adequate in 98.8 % of patients (CI 95 % 93.4–100 %). The success rate on day 3 was 100 %, and the cumulative success rate by day 28 was 98.8 % (CI 95 % 91.7–99.8 %). There were no serious adverse events, with most adverse events classified as mild. The pharmacokinetic parameters of chloroquine analysed in whole blood dry spot samples showed mean (coefficient of variation) Cmax and AUC0–t values of 374.44 (0.35) and 3700.43 (0.36) ng/mL, respectively. Discussion: This study reports an appropriate safety and efficacy profile of a new formulation of coated chloroquine tablets for vivax malaria treatment in the Brazilian Amazon. The cure rates meet the WHO efficacy criteria, supporting current Brazilian guidelines and the use of the formulation for vivax malaria treatment. Nevertheless, further studies should be conducted to address adherence and the effectiveness of the formulation.
Palavras-chave em inglês
MalariaPlasmodium vivax,
Antimalarial treatment
Chloroquine
Pharmacokinetics
Adherence
Clinical trial
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