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Mathematical modelling of malaria chemotherapy: combining artesunate and mefloquine

Published online by Cambridge University Press:  08 October 2002

M. B. HOSHEN ,
W. D. STEIN  and
H. GINSBURG
M. B. HOSHEN
Affiliation:
MALSAT, Liverpool School of Tropical Medicine, The University of Liverpool, Liverpool L69 3BX, UK
W. D. STEIN
Affiliation:
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
H. GINSBURG
Affiliation:
Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
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Abstract

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Clinical data on the use of artesunate combined with mefloquine in a variety of treatment regimens and parasite loads in Thailand were modelled on the basis of experimentally determined pharmacokinetic data. The model assumed no pharmacodynamic interaction between artesunate and mefloquine, but that the parasites were already resistant to mefloquine. Predictions of the model accorded well with the data. In particular, in accordance with clinical observations, the model showed that monotherapy with either drug failed to cure at moderate parasitaemia, yet such patients could be treated effectively with the combination of 3 days of artesunate + mefloquine. For high levels of parasitaemia, 5 days of artesunate+mefloquine were needed. Simulations were also performed for situations of lower resistance to mefloquine and for the immune human populations found in Africa. The importance of mathematical modelling of combination therapy is borne out by this study and suggests its wider application for other drug combinations.

Keywords

artesunatemefloquinecombination therapyPK–PD modelfalciparumresistanceimmunity
Type
Original Article
Information
Parasitology , Volume 124 , Issue 1 , January 2002 , pp. 9 - 15
Copyright
© 2002 Cambridge University Press