Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy.
The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.
Division of Parasitic Diseases & Malaria, Malaria Branch, 1600 Clifton Rd. NE, Mailstop A06, Atlanta, GA 30329, USA. jgutman@cdc.gov
Julie
J
Gutman
S Patrick
SP
Kachur
Laurence
L
Slutsker
Alexis
A
Nzila
Theonest
T
Mutabingwa
D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000517:prevention & control*; D011339:Probenecid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011339:Probenecid; D011739:Pyrimethamine