Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants.
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 2...
| Главные авторы: | , , , , , , , , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
2013
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| _version_ | 1826306428585902080 |
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| author | Creek, D Bigira, V McCormack, S Arinaitwe, E Wanzira, H Kakuru, A Tappero, J Sandison, T Lindegardh, N Nosten, F Aweeka, F Parikh, S |
| author_facet | Creek, D Bigira, V McCormack, S Arinaitwe, E Wanzira, H Kakuru, A Tappero, J Sandison, T Lindegardh, N Nosten, F Aweeka, F Parikh, S |
| author_sort | Creek, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:47:50Z |
| format | Journal article |
| id | oxford-uuid:fb764247-e1db-41c4-ae70-fb9abda808e4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:47:50Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:fb764247-e1db-41c4-ae70-fb9abda808e42022-03-27T13:14:01ZPharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fb764247-e1db-41c4-ae70-fb9abda808e4EnglishSymplectic Elements at Oxford2013Creek, DBigira, VMcCormack, SArinaitwe, EWanzira, HKakuru, ATappero, JSandison, TLindegardh, NNosten, FAweeka, FParikh, SBACKGROUND: 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. |
| spellingShingle | Creek, D Bigira, V McCormack, S Arinaitwe, E Wanzira, H Kakuru, A Tappero, J Sandison, T Lindegardh, N Nosten, F Aweeka, F Parikh, S Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title | Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title_full | Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title_fullStr | Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title_full_unstemmed | Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title_short | Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. |
| title_sort | pharmacokinetic predictors for recurrent malaria after dihydroartemisinin piperaquine treatment of uncomplicated malaria in ugandan infants |
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