Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Australia.
J Infect Dis. 2013 Jun 1;207(11):1646-54. doi: 10.1093/infdis/jit078. Epub 2013 Feb 27.
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.
虽然双氢青蒿素-哌喹（DP）主要用于儿童，但缺乏 DP 在幼儿中使用的药代动力学/药效学（PK/PD）数据。
我们在乌干达对 107 名幼儿进行了哌喹的前瞻性 PK/PD 研究。在长达 5 个月的随访期间，共发生了 218 例疟疾治疗后，在治疗后 28 天内采集了样本。疟疾随访主动进行到第 28 天，被动进行到第 63 天。
治疗后第 7 天，毛细血管哌喹的中位数浓度为 41.9ng/mL。低哌喹浓度与 42 天内复发性疟疾的风险增加相关，主要发生在接受甲氧苄啶-磺胺甲恶唑（TMP-SMX）预防的儿童中。在未接受 TMP-SMX 的儿童中，低哌喹浓度与复发性疟疾的风险增加仅略有相关。然而，对于接受 TMP-SMX 的儿童，相关性很强，在所有采样日都很明显，第 7 天哌喹浓度≤27.3ng/mL 与复发性疟疾的风险大大增加相关。值得注意的是，在 132 例复发性疟疾中，119 例在复发性疟疾发作时检测到哌喹浓度可检测到。
这些哌喹 PK/PD 数据代表了<2 岁儿童中的首次研究。TMP-SMX 预防的儿童在 DP 治疗后第 7 天的哌喹暴露与复发性疟疾的风险增加相关。有趣的是，尽管存在强烈的关联，婴儿仍然存在疟疾风险，即使他们有哌喹的残留水平。
