%0 Journal Article %1 Creek2013c %A Creek, Darren J. %A Bigira, Victor %A McCormack, Shelley %A Arinaitwe, Emmanuel %A Wanzira, Humphrey %A Kakuru, Abel %A Tappero, Jordan W. %A Sandison, Taylor G. %A Lindegardh, Niklas %A Nosten, Francois %A Aweeka, Francesca T. %A Parikh, Sunil %D 2013 %J J Infect Dis %K antimalarials malaria dosing falciparum %N 11 %P 1646--1654 %R 10.1093/infdis/jit078 %T Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. %U http://dx.doi.org/10.1093/infdis/jit078 %V 207 %X Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.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.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.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.

@article{Creek2013c, abstract = {Although dihydroartemisinin-piperaquine (DP) is used primarily in children, pharmacokinetic/pharmacodynamic (PK/PD) data on DP use in young children are lacking.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.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.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.}, added-at = {2013-08-19T02:45:56.000+0200}, author = {Creek, Darren J. and Bigira, Victor and McCormack, Shelley and Arinaitwe, Emmanuel and Wanzira, Humphrey and Kakuru, Abel and Tappero, Jordan W. and Sandison, Taylor G. and Lindegardh, Niklas and Nosten, Francois and Aweeka, Francesca T. and Parikh, Sunil}, biburl = {https://www.bibsonomy.org/bibtex/2a086abde35ae4f0494243e9a498786ac/aorchid}, description = {paper copy. Levels do correlate with reinfection risk. Also, most had detectable piperaquine at the time of recurrence. I suspect that the piperaquine in DP will not last that long. But that seems logical give the long, unprotected tail. One could have easily predicted as much, we'll see.}, doi = {10.1093/infdis/jit078}, groups = {public}, institution = {Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia.}, interhash = {06e49d908a16b678d09bc0e5a4837676}, intrahash = {a086abde35ae4f0494243e9a498786ac}, journal = {J Infect Dis}, keywords = {antimalarials malaria dosing falciparum}, language = {eng}, medline-pst = {ppublish}, month = Jun, number = 11, pages = {1646--1654}, pii = {jit078}, pmid = {23447696}, timestamp = {2013-08-19T02:45:56.000+0200}, title = {Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants.}, url = {http://dx.doi.org/10.1093/infdis/jit078}, username = {aorchid}, volume = 207, year = 2013 }