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https://www.arca.fiocruz.br/handle/icict/67916
EFFICACY OF ARTESUNATE-MEFLOQUINE COMBINATION THERAPY ON SURVIVAL IN PLASMODIUM BERGHEI-INFECTED MICE: A TIME-TO-EVENT ANALYSIS
Malaria
Plasmodium berghei
Plasmodium falciparum
Antimalarial drug combination
Author
Affilliation
Universidade Federal da Bahia. Programa de Pós-Graduação em Farmácia, Faculdade de Farmácia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Federal da Bahia. Programa de Pós-Graduação em Farmácia, Faculdade de Farmácia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Estadual da Bahia. Faculdade de Engenharia de Bioprocessos e Biotecnologia. Departamento de Tecnologia e Ciências Sociais. Juazeiro, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Center for Pharmacometrics & System Pharmacology. College of Pharmacy. University of Florida. Orlando, FL, United States.
Universidade Federal da Bahia. Programa de Pós-Graduação em Farmácia, Faculdade de Farmácia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Estadual da Bahia. Faculdade de Engenharia de Bioprocessos e Biotecnologia. Departamento de Tecnologia e Ciências Sociais. Juazeiro, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Center for Pharmacometrics & System Pharmacology. College of Pharmacy. University of Florida. Orlando, FL, United States.
Abstract
Artesunate-mefloquine combination therapy (AR-MQ) is a standard therapy for treating uncomplicated malaria by Plasmodium falciparum. Time-to-event (TTE) analysis is used to describe the occurrence and timing of events by yielding information about the risk of an event occurring during a specific period. Therefore, the aim of the present study is to evaluate the efficacy of AR-MQ combination therapy on the survival time of Plasmodium berghei-infected mice using TTE analysis. Here, TTE analysis was used to analyze P. berghei-infected mice receiving a single oral dose of 100 mg/kg artesunate and 55 mg/kg mefloquine or dose-matched artesunate monotherapy. Median survival was higher for AR-MQ than for monotherapy. A survival analysis to evaluate the influence of treatment on survival was performed using MonolixSuite™. The Weibull model best described the mortality time of the animals. Subsequent analysis identified that AR-MQ had a significant influence on population survival time (Te_pop), estimated at 13.66 days, population parameter for curve fitting (p_pop) at 4.39, and survival time under AR-MQ treatment (beta Te_AR-MQ) at 0.77 days. The probability of survival 7, 15, and 30 days after treatment with AR-MQ was 94.4%, 88.9%, and 14.9%, respectively. The experimental and modeling data both found that AR-MQ combination therapy yielded increased survival of infected animals.
Keywords
Survival analysisMalaria
Plasmodium berghei
Plasmodium falciparum
Antimalarial drug combination
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