Table 1 |
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Pharmacology of selected candidates for IPTp |
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Drug |
Mode of action |
Elimination half life |
Advantages/disadvantages |
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Artemether |
Inhibits falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase |
3 – 7 h (converted to DHA) |
Appears safe in the second and third trimester Widely available in a cheap, fixed dose co-formulation with lumefantrine (Coartem©/Riamet©) |
|
Artemisinin |
Inhibits falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase |
2 – 3 h (converted to DHA) |
Appears safe in the second and third trimester Fixed dose co-formulations unavailable |
|
Artesunate |
Inhibits falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase |
2 – 5 mins (converted to DHA) |
Appears safe in the second and third trimester Fixed dose co-formulations unavailable |
|
Atovaquone |
Selective inhibitor of parasite mitochondrial metabolism |
48 – 72 h |
Appears safe in the third trimester Available only in fixed dose co-formulation with proguanil (Malarone©), which is expensive outside specific donation programmes |
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Azithromycin |
Exact mode of action unknown |
68 h |
Safe in all trimesters where has been used extensively in STI treatment Expensive; fixed dose co-formulations unavailable |
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Chlorproguanil |
Folic acid antagonist (inhibits dihydrofolate reductase) |
32 h |
Cheap; appears safe in the third trimester and likely to be safe earlier in pregnancy based on experience with proguanil Available only in fixed dose co-formulation with dapsone (Lapdap©), which WHO have recommended be used with caution in areas of high G6PD deficiency |
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Dapsone |
Folic acid antagonist (inhibits dihydropteroate synthase) |
31 h |
Cheap; appears safe in the third trimester Available in fixed dose co-formulation with chlorproguanil (Lapdap©), which WHO have recommended be used with caution in areas of high G6PD deficiency |
|
Dihydroartemisinin (DHA) |
Inhibits falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase |
40 – 60 mins |
Likely to be safe in the second and third trimester Available in SE Asia, China in a cheap fixed dose co-formulation with piperaquine (Artekin©/Eurartekin©) |
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Lumefantrine |
Inhibits metabolism of haem within parasite acid food vacuole |
4 – 6 days |
Safety in children and adults established but no data available in pregnancy Widely available in a cheap [through WHO pricing agreement], fixed dose co-formulation with artemether (Coartem©/Riamet©) |
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Mefloquine |
Exact mode of action unknown |
2 – 4 weeks |
Appears safe in the second and third trimester Expensive; fixed dose co-formulations unavailable |
|
Piperaquine |
Inhibits detoxification of haem |
3 – 4 weeks |
Safety in children and adults established but no data available in pregnancy Available in SE Asia, China in a cheap, fixed dose co-formulation with dihydroartemisinin (Artekin©/Eurartekin©) |
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Proguanil |
Folic acid antagonist (inhibits dihydrofolate reductase) |
12 – 21 h |
Cheap; appears safe in all trimesters Available alone or in fixed dose co-formulation with atovaquone (Malarone©), which is expensive outside specific donation programmes |
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Pyrimethamine |
Folic acid antagonist (inhibits dihydrofolate reductase) |
100 h |
Cheap; widely available in fixed-dose combination with sulphadoxine Increasing resistance particularly in East Africa |
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Sulphadoxine |
Folic acid antagonist (inhibits dihydropteroate synthase) |
200 h |
Cheap; widely available in fixed-dose combination with pyrimethamine Increasing resistance particularly in East Africa |
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Vallely et al. Malaria Journal 2007 6:16 doi:10.1186/1475-2875-6-16 |
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