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NEJM：新一代抗疟药物KAF156显示出较好的抗疟活性和安全性

2016-09-26 MedSci MedSci原创

KAF156疟原虫抗疟活性
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KAF156是一种新型的抗疟药物类（imidazolopiperazines），在疟原虫蔓延至血液之前或之中，以及红前期肝阶段都具有活性。研究人员在泰国和越南的5个中心进行了一项2期、开放式标签研究来评估成人急性间日疟原虫和恶性疟原虫感染使用抗疟药物KAF156的疗效及安全性。评估患者经抗疟治疗后的寄生虫清除率，间日疟原虫或恶性疟原虫感染的患者给予多剂量抗疟药治疗（400毫克/日，3天），接着评估

KAF156是一种新型的抗疟药物类（imidazolo piperazines），在疟原虫蔓延至血液之前或之中，以及红前期阶段都具有活性。

研究人员在泰国和越南的5个中心进行了一项2期、开放式标签研究来评估成人急性间日疟原虫和恶性疟原虫感染使用抗疟药物KAF156的疗效及安全性。评估患者经抗疟治疗后的寄生虫清除率，间日疟原虫或恶性疟原虫感染的患者给予多剂量抗疟药治疗（400毫克/日，3天），接着评估另一个接受单独队列的恶性疟疾患者，接受单剂量治疗（800毫克），评估是在治疗第28天。

结果10名恶性疟疾患者的中位原虫清除时间为45小时（四分位距为42-48），10名间日疟原虫患者经多剂量抗疟治疗后的中位原虫清除时间为24小时（四分位距为20-30），21名恶性疟疾患者经单剂量抗疟治疗后的中位原虫清除时间为49小时后（四分位距为42-54）。这21名恶性疟疾患者随访28天期间，1例再次感染和7例复发性感染（治愈率，67%；95%可信区间，46-84）。平均（±SD）KAF156末端消除半衰期为44.1±8.9小时。在这个小型研究中并没有严重不良事件的发生。最常见的不良事件包括窦性心动过缓、血小板减少症、低钾血症、贫血和高胆红素血症。2名患者发生2级或更高级的不良反应，1名患者由于接受800毫克单剂量后出现反复呕吐而停止治疗。单剂量组中不良反应事件的发生率更高，但是随访时间较多剂量组长。

总而言之，该小型研究发现在此无合并症的间日疟原虫和恶性疟原虫感染成人患者中KAF156具有抗疟活性，未发现安全问题。


小知识：
2014年，由诺华热带疾病研究所(Novartis Institute for Tropical Diseases)负责人蒂埃里•迪亚贾纳(Thierry Diagana)博士领导的诺华热带疾病研究所展示了一种治疗疟疾的新药的首次临床概念验证（显示药物有效的临床试验）。这种复方药物的代号是KAE 609，它通过干扰引发大部分疟疾病例的两种寄生虫体内的纳浓度而起到治疗作用。间日疟原虫(Plasmodium vivax)在亚洲和南美较为普遍，而毒性更大的恶性疟原虫(Plasmodium falciparum)在非洲最为普遍。重要的是，KAE 609对于东南亚那些携带青蒿素抗药性菌株的人也有疗效。

第二种复方药物KAF 156,为一种咪唑-哌嗪类复合物（imidazolo-piperazine compound）。它有望抵御两种寄生虫的抗药菌株，并具有另一种独特优势。与基于青蒿素的疗法不同，KAF 156可以在疟疾的无症状“肝脏期”、在疾病蔓延到血流之前杀灭寄生虫。

原始出处：

Nicholas J. White,.et al., Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med 2016; 375:1152-1160September 22, 2016DOI: 10.1056/NEJMoa1602250.
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    2016-10-13 1e10c84am36(暂无匿称)

    文章真好，喜欢阅读

    0

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    2016-10-11 1e10c84am36(暂无匿称)

    好文章，长见识

    0

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createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-11-06 wushaoling

    #抗疟药#

    0

  4. 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createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:02:34 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1951541, encodeId=4a3519515416b, content=<a href='/topic/show?id=aeeb5545681' target=_blank style='color:#2F92EE;'>#抗疟药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55456, encryptionId=aeeb5545681, topicName=抗疟药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Sun Nov 06 15:30:00 CST 2016, time=2016-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=138198, encodeId=48ef138198a3, content=很好的了解一下疟疾！, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Fri Sep 30 17:26:10 CST 2016, time=2016-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=138197, encodeId=37c513819eb2, content=学习了，分享一下！, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Fri Sep 30 17:25:47 CST 2016, time=2016-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135615, encodeId=120513561591, content=继续关注！, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:18 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135614, encodeId=d847135614c9, content=谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:12 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135580, encodeId=078e135580cd, content=非常值得学习，要重视, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cd381919282, createdName=1e0a2178m68(暂无匿称), createdTime=Mon Sep 26 21:00:41 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135425, encodeId=bfc913542541, content=厉害的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Mon Sep 26 13:28:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135423, encodeId=94ab13542316, content=学习了，赞一个！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-30 1e0d99ddm02(暂无匿称)

    很好的了解一下疟疾！

    0

  5. 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createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:18 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135614, encodeId=d847135614c9, content=谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:12 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135580, encodeId=078e135580cd, content=非常值得学习，要重视, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cd381919282, createdName=1e0a2178m68(暂无匿称), createdTime=Mon Sep 26 21:00:41 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135425, encodeId=bfc913542541, content=厉害的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Mon Sep 26 13:28:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135423, encodeId=94ab13542316, content=学习了，赞一个！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-30 1e0d99ddm02(暂无匿称)

    学习了，分享一下！

    0

  6. 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createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:18 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135614, encodeId=d847135614c9, content=谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:12 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135580, encodeId=078e135580cd, content=非常值得学习，要重视, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cd381919282, createdName=1e0a2178m68(暂无匿称), createdTime=Mon Sep 26 21:00:41 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135425, encodeId=bfc913542541, content=厉害的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Mon Sep 26 13:28:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135423, encodeId=94ab13542316, content=学习了，赞一个！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-26 知难而进

    继续关注！

    0

  7. 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createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:02:34 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1951541, encodeId=4a3519515416b, content=<a href='/topic/show?id=aeeb5545681' target=_blank style='color:#2F92EE;'>#抗疟药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55456, encryptionId=aeeb5545681, topicName=抗疟药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca20190, createdName=wushaoling, createdTime=Sun Nov 06 15:30:00 CST 2016, time=2016-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=138198, encodeId=48ef138198a3, content=很好的了解一下疟疾！, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:18 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135614, encodeId=d847135614c9, content=谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Mon Sep 26 21:29:12 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135580, encodeId=078e135580cd, content=非常值得学习，要重视, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cd381919282, createdName=1e0a2178m68(暂无匿称), createdTime=Mon Sep 26 21:00:41 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135425, encodeId=bfc913542541, content=厉害的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Mon Sep 26 13:28:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135423, encodeId=94ab13542316, content=学习了，赞一个！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-26 知难而进

    谢谢分享！

    0

  8. 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createdBy=cd381919282, createdName=1e0a2178m68(暂无匿称), createdTime=Mon Sep 26 21:00:41 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135425, encodeId=bfc913542541, content=厉害的研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Mon Sep 26 13:28:00 CST 2016, time=2016-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=135423, encodeId=94ab13542316, content=学习了，赞一个！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-26 1e0a2178m68(暂无匿称)

    非常值得学习，要重视

    0

  9. 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createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-26 oo902

    厉害的研究

    0

  10. 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createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Mon Sep 26 13:12:00 CST 2016, time=2016-09-26, status=1, ipAttribution=)]
    2016-09-26 1dd8a7c5m95(暂无匿称)

    学习了，赞一个！！！

    0

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