Abstract | BACKGROUND: 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.
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Authors | Darren 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 |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 207
Issue 11
Pg. 1646-54
(Jun 01 2013)
ISSN: 1537-6613 [Electronic] United States |
PMID | 23447696
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimalarials
- Artemisinins
- Quinolines
- artenimol
- Trimethoprim, Sulfamethoxazole Drug Combination
- piperaquine
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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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