RP-HPLC法测定小鼠血浆中蒿甲醚的浓度

目的建立测定小鼠血浆中蒿甲醚浓度的方法。方法采用RP-HPLC法,色谱柱为Diamonsil C18柱(150 mm×4.6 mm,5μm),流动相为甲醇-水(体积比85∶15);流速为1.0 mL/min;检测波长为210 nm;柱温为室温。利用甲基叔丁基醚对小鼠血浆及组织中蒿甲醚及蒿乙醚进行提取后进行测定。结果蒿甲醚与蒿乙醚的色谱峰分离良好并且出峰时间相近,以蒿乙醚为内标测定血浆中蒿甲醚符合方法学要求,血浆标准曲线在一定范围内线性关系良好(R2=0.9991,n=5),高、中、低3个浓度的回收率均为97%以上,日内及日间RSD均小于3%。结论建立的方法可简单快速测定蒿甲醚在小鼠血浆中的浓度,为内标法测定蒿甲醚在动物血浆中的浓度提供思路。     

蒿甲醚对约氏疟原虫在斯氏按蚊体内发育影响

目的 研究蒿甲醚对约氏疟原虫在大劣按蚊体内发育的影响及其机制.方法 本课题利用已经建立的斯氏按蚊-约氏疟原虫模型,通过吸饲蒿甲醚糖水的方法,观察蒿甲醚是否影响约氏疟原虫在斯氏按蚊体内的发育.通过RT-PCR方法,分析NOS、TEP1和PPO三个斯氏按蚊重要的免疫反应相关基因的表达变化,以了解青蒿素类药物蒿甲醚影响疟原虫...     

蒿甲醚早期治疗小鼠血吸虫病的疗效(英文)

蒿甲醚（Ａｒｔ）系青蒿素的衍生物，不仅有抗疟作用，还有抗血吸虫（特别是ｄ７童虫）作用。本文应用Ａｒｔ的早期治疗方案，观察其控制血吸虫感染的可能性。结果表明小鼠于感染日本血吸虫尾蚴当天（ｄｏ）ｉｇＡｒｔ３００ｍｇ．ｋｇ－１，然后每隔２－３ｗｋｉｇ１次相同剂量的Ａｒｔ时，减虫率和减雌虫率均低。若于感染后ｄ７开始ｉｇ首剂Ａｒｔ，然后每ｗｋｉｇ１次，共给４次时，可使宿主体内的雌虫减少近９０％或９０％以上，且部分鼠的雌虫被完全消灭，肝脏亦无明显变化。此外，ｄ７童虫经Ａｒｔ３００ｍｇ·ｋｇ－１作用后，残留的雌虫发育缓慢，治后３ｗｋ（即感染后２８ｄ），大部分雌虫的生殖腺尚未发育成熟，少数虽已发育，但其子宫内的虫卵数较对照组的减少９１．７％。表明Ａｒｔ用于感染血吸虫尾蚴后早期治疗，可起到保护宿主的作用，不仅可控制血吸虫感染，而且还可减轻感染度。     

In vitro evaluation of the cytotoxic and genotoxic effects of artemether,an antimalarial drug,in a gastric cancer cell line (PG100)

Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose‐dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml^?1 (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml^?1, for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml^?1, for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. Copyright © 2011 John Wiley & Sons, Ltd.     

蒿甲醚在兔体内的药代动力学

本文报道蒿甲醚在兔体内的药代动力学。静脉输注蒿甲醚脂肪乳剂(蒿甲醚80mg/kg)后,血药时间数据用NONLIN程序拟合曲线,符合线性二室开模型。药代动力学参数的平均(SD)为:t1/2(α和β)分别为0.144(0.077)h和0.896(0.371)h;k₂₁,k₁₀和k₁₂分别为1.235(0.705),4.143(1.370)和1.140(0.951)h^-1;V_c,V_d(area)和V_d(ss)分别为0.609(0.119),2.985(0.787)和1.054(0.202)L/kg;清除率为2.401(0.339)L·kg^-1·h。肌内注射油剂250mg/kg或125mg/kg,血药时间数据按矩量法计算,得吸收速率常数(Ka)为0.0377(0.0119)h^-1;吸收程度为36.14(18.39)%。     

Use of artemether–lumefantrine to treat malaria during pregnancy: what do we know and need to know?

Artemether–lumefantrine is a fixed-dose combination containing 20 mg artemether/120 mg lumefantrine per tablet, used for treating uncomplicated malaria in patients weighing ≥5 kg. It is the first artemisinin-based combination registered in some European countries and in the USA. It is marketed in Europe as Riamet^® (Novartis, Basel, Switzerland) and in malaria-endemic countries as Coartem^® (Novartis). Safety concerns prevent early pregnancy usage, while limited postmarketing surveillance has delayed safety assessment and policy development. Large clinical studies, postmarketing surveillance and pharmacovigillance ongoing in some countries may soon bridge safety issues. Fatty diet requirements for optimal absorption, pregnancy-induced changes in pharmacokinetics, pregnancy-related anorexia and food taboos, and emerging reduced parasite sensitivity to artemisinin, challenges optimal artemether–lumefantrine dosing and efficacy during pregnancy. This evaluation addresses drug usage, safety concerns following early exposure, implications for changed pharmacokinetics and reduced parasite susceptibility. Clinical-use updates and strategies to address some knowledge gaps including key operational research are discussed.     

蒿甲醚体外抗多房棘球绦虫原头蚴作用研究

目的观察蒿甲醚体外抗多房棘球绦虫原头蚴作用,探讨治疗泡球蚴病新药物。方法将多房棘球绦虫原头蚴随机分为4组：蒿甲醚低剂量组（50μg/ml）,蒿甲醚高剂量组（100μg/ml）,阿苯达唑组（50μg/ml）,空白对照组。每组设2个平行组,每组约含3 000个原头节,分别置含10 ml DMEM培养液的培养瓶中,每天观察1次,取样滴于玻片,用0.03%美蓝染色,显微镜下计数原头蚴约200个,计算死亡率。直至该组原头蚴全部死亡时培养结束,并对原头蚴进行超微结构观察。结果蒿甲醚50μg/ml和100μg/ml组不同作用时间原头蚴死亡率与空白对照组相比差异均有统计学意义（P〈0.05）;高、低剂量组原头蚴死亡率差异无统计学意义（P〉0.05）。培养至第9 d时,蒿甲醚高剂量组原头蚴死亡率达100%,蒿甲醚低剂量组原头蚴死亡率93.28%,阿苯达唑组原头蚴死亡率99.03%,空白对照组原头蚴死亡率78.83%。结论蒿甲醚具有体外抗多房棘球绦虫原头蚴作用,且呈剂量、时间依赖。     

Translation of artemether-lumefantrine treatment policy into paediatric clinical practice: an early experience from Kenya

Objective To describe the quality of outpatient paediatric malaria case‐management approximately 4–6 months after artemether–lumefantrine (AL) replaced sulfadoxine–pyrimethamine (SP) as the nationally recommended first‐line therapy in Kenya. Methods Cross‐sectional survey at all government facilities in four Kenyan districts. Main outcome measures were health facility and health worker readiness to implement AL policy; quality of antimalarial prescribing, counselling and drug dispensing in comparison with national guidelines; and factors influencing AL prescribing for treatment of uncomplicated malaria in under‐fives. Results We evaluated 193 facilities, 227 health workers and 1533 sick‐child consultations. Health facility and health worker readiness was variable: 89% of facilities stocked AL, 55% of health workers had access to guidelines, 46% received in‐service training on AL and only 1% of facilities had AL wall charts. Of 940 children who needed AL treatment, AL was prescribed for 26%, amodiaquine for 39%, SP for 4%, various other antimalarials for 8% and 23% of children left the facility without any antimalarial prescribed. When AL was prescribed, 92% of children were prescribed correct weight‐specific dose. AL dispensing and counselling tasks were variably performed. Higher health worker’s cadre, in‐service training including AL use, positive malaria test, main complaint of fever and high temperature were associated with better prescribing. Conclusions Changes in clinical practices at the point of care might take longer than anticipated. Delivery of successful interventions and their scaling up to increase coverage are important during this process; however, this should be accompanied by rigorous research evaluations, corrective actions on existing interventions and testing cost‐effectiveness of novel interventions capable of improving and maintaining health worker performance and health systems to deliver artemisinin‐based combination therapy in Africa.