Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar.
Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar.
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DOI：
10.1186/s12936-018-2278-5
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发表时间：
2018-03-23
期刊：
影响因子：
3
通讯作者：
Tarning J
中科院分区：
文献类型：
--
作者：
Lohy Das JP;Kyaw MP;Nyunt MH;Chit K;Aye KH;Aye MM;Karlsson MO;Bergstrand M;Tarning J
青蒿素是治疗简单和严重恶性疟原虫疟疾最有效的抗疟药物。然而，东南亚大湄公河地区广泛存在的青蒿素耐药性正在威胁控制和消除疟疾的可能性。这项工作旨在评估青蒿琥酯及其活性代谢产物双氢青蒿素在缅甸南部敏感和耐药恶性疟原虫感染患者中的药代动力学和药效学特性。此外，还评价了以前为确定青蒿素耐药疟疾感染而开发的简单列线图。招募了53名患者，每天口服青蒿琥酯单药治疗（4 mg/kg），持续7天。频繁青蒿琥酯和双氢青蒿素血浆浓度测量和寄生虫显微镜计数，并使用非线性混合效应模型进行评价。青蒿琥酯的吸收是最好的特点是一个过渡室（n = 3）模型，其次是青蒿琥酯和双氢青蒿素的一室处置模型。使用Emax函数描述了双氢青蒿素的药物依赖性寄生虫杀灭作用，混合模型区分青蒿素敏感和耐药寄生虫。总体而言，预计56%的研究人群患有耐药性疟疾感染。应用拟议的诺模图来识别青蒿素耐药性疟疾感染，表明总体灵敏度为90%，而传统的第3天阳性检测为55%。青蒿琥酯和双氢青蒿素的药代动力学-药效学特性用混合物模型进行了充分表征，以区分这些患者中的药物敏感性和耐药性感染。这项研究招募的所有患者中有一半以上患有青蒿素耐药感染。建议诺模图的相对较高的灵敏度突出了其潜在的临床实用性。
Artemisinins are the most effective anti-malarial drugs for uncomplicated and severe Plasmodium falciparum malaria. However, widespread artemisinin resistance in the Greater Mekong Region of Southeast Asia is threatening the possibility to control and eliminate malaria. This work aimed to evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its active metabolite, dihydroartemisinin, in patients with sensitive and resistant falciparum infections in Southern Myanmar. In addition, a simple nomogram previously developed to identify artemisinin resistant malaria infections was evaluated. Fifty-three (n = 53) patients were recruited and received daily oral artesunate monotherapy (4 mg/kg) for 7 days. Frequent artesunate and dihydroartemisinin plasma concentration measurements and parasite microscopy counts were obtained and evaluated using nonlinear mixed-effects modelling. The absorption of artesunate was best characterized by a transit-compartment (n = 3) model, followed by one-compartment disposition models for artesunate and dihydroartemisinin. The drug-dependent parasite killing effect of dihydroartemisinin was described using an Emax function, with a mixture model discriminating between artemisinin sensitive and resistant parasites. Overall, 56% of the studied population was predicted to have resistant malaria infections. Application of the proposed nomogram to identify artemisinin-resistant malaria infections demonstrated an overall sensitivity of 90% compared to 55% with the traditional day-3 positivity test. The pharmacokinetic-pharmacodynamic properties of artesunate and dihydroartemisinin were well-characterized with a mixture model to differentiate between drug sensitive and resistant infections in these patients. More than half of all patients recruited in this study had artemisinin-resistant infections. The relatively high sensitivity of the proposed nomogram highlights its potential clinical usefulness.
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影响因子：
6.1
作者：
Lindbom, L;Pihlgren, P;Jonsson, N
通讯作者：
Jonsson, N
DOI：
10.1016/j.jpba.2007.04.030
发表时间：
2007-09-21
影响因子：
3.4
作者：
Lindegardh, N.;Dondorp, A. M.;Day, N. P. J.
通讯作者：
Day, N. P. J.
影响因子：
4.9
作者：
Lourens, Chris;Lindegardh, Niklas;Tarning, Joel
通讯作者：
Tarning, Joel
影响因子：
2.5
作者：
Gisleskog, PO;Karlsson, MO;Beal, SL
通讯作者：
Beal, SL
DOI：
10.1016/s1473-3099(17)30048-8
发表时间：
2017-05
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Imwong M;Suwannasin K;Kunasol C;Sutawong K;Mayxay M;Rekol H;Smithuis FM;Hlaing TM;Tun KM;van der Pluijm RW;Tripura R;Miotto O;Menard D;Dhorda M;Day NPJ;White NJ;Dondorp AM
通讯作者：
Dondorp AM