Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.
Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.
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DOI：
10.1093/infdis/jiw338
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发表时间：
2016-10-15
期刊：
影响因子：
--
通讯作者：
Parikh S
中科院分区：
文献类型：
--
作者：
Tchaparian E;Sambol NC;Arinaitwe E;McCormack SA;Bigira V;Wanzira H;Muhindo M;Creek DJ;Sukumar N;Blessborn D;Tappero JW;Kakuru A;Bergqvist Y;Aweeka FT;Parikh S
背景：本芴醇是最广泛使用的疟疾治疗药物蒿甲醚-本芴醇的一种成分，其药代动力学和药效学尚未在幼儿中得到充分表征。 方法：在105名乌干达儿童中测定毛细血管全血本芴醇浓度和治疗结果，这些儿童年龄在6个月到2岁之间，他们用蒿甲醚-本芴醇治疗了249次恶性疟原虫疟疾。 结果：本芴醇的群体药代动力学采用一级吸收的二室开放模型。 在一个模型中，年龄与生物利用度有显着的正相关性，包括异速生长缩放。未接受甲氧苄啶-磺胺甲恶唑治疗的儿童，毛细血管全血浓度<200 ng/mL，与浓度>200 ng/mL的儿童相比，28天复发性寄生虫血症的风险高3倍（P = .0007）。然而，对于接受甲氧苄啶-磺胺甲恶唑治疗的儿童，在此阈值的基础上，复发性寄生虫血症的风险没有显著差异。第3天的浓度比第7天的浓度更能预测28天的复发。结论：我们证明，除体重外，年龄也是本芴醇暴露的决定因素，在没有甲氧苄啶-磺胺甲恶唑的情况下，本芴醇暴露是复发性寄生虫血症的决定因素。 6个月至2岁儿童的接触水平一般低于公布的年龄较大儿童和成人的接触水平。可能需要进一步改进蒿甲醚-苯芴醇的剂量，以改善婴儿和幼儿的暴露。
Background. The pharmacokinetics and pharmacodynamics of lumefantrine, a component of the most widely used treatment for malaria, artemether-lumefantrine, has not been adequately characterized in young children. Methods. Capillary whole-blood lumefantrine concentration and treatment outcomes were determined in 105 Ugandan children, ages 6 months to 2 years, who were treated for 249 episodes of Plasmodium falciparum malaria with artemether-lumefantrine. Results. Population pharmacokinetics for lumefantrine used a 2-compartment open model with first-order absorption. Age had a significant positive correlation with bioavailability in a model that included allometric scaling. Children not receiving trimethoprim-sulfamethoxazole with capillary whole blood concentrations <200 ng/mL had a 3-fold higher hazard of 28-day recurrent parasitemia, compared with those with concentrations >200 ng/mL (P = .0007). However, for children receiving trimethoprim-sulfamethoxazole, the risk of recurrent parasitemia did not differ significantly on the basis of this threshold. Day 3 concentrations were a stronger predictor of 28-day recurrence than day 7 concentrations. Conclusions. We demonstrate that age, in addition to weight, is a determinant of lumefantrine exposure, and in the absence of trimethoprim-sulfamethoxazole, lumefantrine exposure is a determinant of recurrent parasitemia. Exposure levels in children aged 6 months to 2 years was generally lower than levels published for older children and adults. Further refinement of artemether-lumefantrine dosing to improve exposure in infants and very young children may be warranted.
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影响因子：
3
作者：
Staehli Hodel EM;Guidi M;Zanolari B;Mercier T;Duong S;Kabanywanyi AM;Ariey F;Buclin T;Beck HP;Decosterd LA;Olliaro P;Genton B;Csajka C
通讯作者：
Csajka C
柬埔寨恶性疟原虫疟疾中的双氢青蒿素-哌喹抗药性：一项多地点前瞻性队列研究。
DOI：
10.1016/s1473-3099(15)00487-9
发表时间：
2016-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amaratunga C;Lim P;Suon S;Sreng S;Mao S;Sopha C;Sam B;Dek D;Try V;Amato R;Blessborn D;Song L;Tullo GS;Fay MP;Anderson JM;Tarning J;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
3.3
作者：
Ashley, Elizabeth A.;Stepniewska, Kasia;Nosten, Francois
通讯作者：
Nosten, Francois
影响因子：
4.9
作者：
Kredo, T.;Mauff, K.;Barnes, K. I.
通讯作者：
Barnes, K. I.
影响因子：
3
作者：
Green, Michael;Otieno, Kephas;Desai, Meghna
通讯作者：
Desai, Meghna