The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses

doi:10.1016/S0169-4758(97)01124-1

Parasitology Today

Volume 13, Issue 12, December 1997, Pages 459-464

Parasitology Today

https://doi.org/10.1016/S0169-4758(97)01124-1 Get rights and content

Abstract

At present, effective treatment for non-severe malaria is the most important malaria control strategy in Africa. Pyrimethamine—sulfadoxine (PSD) is rapidly becoming the first-line treatment in areas of chloroquine resistance, although the parasite chemoresistance factors that dispose towards clinical failure with PSD are still unclear. Here, Bill Watkins and colleagues analyse the relationship between the pharmacokinetic properties of two treatment combinations (PSD and chlorproguanil—dapsone) in vivo and the respective in vitro isobolograms for parasites with specific drug-resistance patterns. From this relationship, they develop a hypothesis that may explain clinical drug failure and differential efficacy between treatments. The deductions can be tested in field studies to validate or refute the model.

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ReviewThe efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses

Abstract

Mol. Biochem. Parasitol.

J. Biol. Chem.

Trans. R. Soc. Trop. Med. Hyg.

Endeavour

Trans. R. Soc. Trop. Med. Hyg.

Parasitol. Today

Mol. Biochem. Parasitol.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Lancet

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Acta Trop.

Biochem. Parasitol.

Trans. R. Soc. Trop. Med. Hyg.

Trans. R. Soc. Trop. Med. Hyg.

Lancet

Chemotherapy of malaria and resistance to antimalarials

Tech. Rep. Series

Folate metabolism in malaria

Bull. WHO

Biochemistry of Plasmodium (malarial parasites)

Microbiol. Rev.

De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite Plasmodium falciparum

Mol. Biochem. Parasitol.

Synergistic antimalarial activity of pyrimethamine and sulfadoxine against Plasmodium falciparum in vitro

Am. J. Trop. Med. Hyg.

In vitro activities of and mechanisms of resistance to antifolate antimalarial drugs

Antimicrob. Agents Chemother.

Measurement of the potencies of drug mixtures

Biometrics

A method for testing synergy with any number of agents

J. Infect. Dis.

Stage-specific sensitivity of Plasmodium falciparum to antifolates

Z. Parasitenkd.

Review
The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses