Progress in the development of piperaquine combinations for the treatment of malaria.
OBJECTIVE
Dihydroartemisinin-piperaquine is a new and extremely promising artemisinin-containing fixed-combination antimalarial, about to be registered with international regulatory authorities such as the European Medicines Agency. A formulation produced according to good manufacturing practices should be available soon.


RESULTS
Piperaquine is characterized by a slow absorption, long mean terminal elimination half-life and large mean volume distribution. However, children, compared to the population mean profile, tend to have a smaller central volume of distribution, a shorter distribution half-life and a more rapid fall in early piperaquine plasma concentrations, suggesting that an increase of the weight-adjusted dosage in children may be required. In addition, the oral bioavailability of piperaquine improves when given with a high-fat meal, though this does not necessarily translate into a higher efficacy. Several clinical trials have repeatedly shown that dihydroartemisinin-piperaquine is well tolerated and efficacious, with the only exception of one trial recently carried out in Papua New Guinea. Patients treated with dihydroartemisinin-piperaquine may have a higher rate of person-gametocyte-weeks, though it is unclear whether this translates into a higher infectiousness to biting anophelines.


CONCLUSIONS
The dosage recommended for children may need to be reviewed and the usefulness of the coadministration with food should be determined. Establishing safety and efficacy of this treatment in pregnancy remains a priority.
Institute of Tropical Medicine, Antwerp, Belgium. udalessandro@itg.be
Umberto
U
D'alessandro
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics / Q000627:therapeutic use*; D037621:Artemisinins / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines