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Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants.

AbstractBACKGROUND:
Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.
METHODS:
We conducted a prospective PK/PD study of piperaquine in 107 young children in Uganda. Samples were collected up to 28 days after 218 episodes of malaria treatment, which occurred during follow-up periods of up to 5 months. Malaria follow-up was conducted actively to day 28 and passively to day 63.
RESULTS:
The median capillary piperaquine concentration on day 7 after treatment was 41.9 ng/mL. Low piperaquine concentrations were associated with an increased risk of recurrent malaria for up to 42 days, primarily in those receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. In children not receiving TMP-SMX, low piperaquine concentrations were only modestly associated with an increased risk of recurrent malaria. However, for children receiving TMP-SMX, associations were strong and evident for all sampling days, with PQ concentrations of ≤ 27.3 ng/mL on day 7 associated with a greatly increased risk of recurrent malaria. Notably, of 132 cases of recurrent malaria, 119 had detectable piperaquine concentrations at the time of presentation with recurrent malaria.
CONCLUSIONS:
These piperaquine PK/PD data represent the first in children <2 years of age. Piperaquine exposure on day 7 correlated with an increased risk of recurrent malaria after DP treatment in children receiving TMP-SMX prophylaxis. Interestingly, despite strong associations, infants remained at risk for malaria, even if they had residual levels of piperaquine.
AuthorsDarren J Creek, Victor Bigira, Shelley McCormack, Emmanuel Arinaitwe, Humphrey Wanzira, Abel Kakuru, Jordan W Tappero, Taylor G Sandison, Niklas Lindegardh, Francois Nosten, Francesca T Aweeka, Sunil Parikh
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 11 Pg. 1646-54 (Jun 01 2013) ISSN: 1537-6613 [Electronic] United States
PMID23447696 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antimalarials
  • Artemisinins
  • Quinolines
  • artenimol
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • piperaquine
Topics
  • Antimalarials (administration & dosage, pharmacokinetics)
  • Artemisinins (administration & dosage, pharmacokinetics)
  • Chemoprevention (methods)
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Malaria (drug therapy, prevention & control)
  • Male
  • Plasma (chemistry)
  • Prospective Studies
  • Quinolines (administration & dosage, pharmacokinetics)
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination (administration & dosage)
  • Uganda

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