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Antimicrob Agents Ch:HIV儿童:洛匹那韦-利托那韦与MDR-TB常用药联用时相互作用如何?

2018-03-02 谈志远,王淳 环球医学

2018年1月,发表在《Antimicrob Agents Chemother》上的一项研究,对洛匹那韦-利托那韦与一线和二线抗结核药物在艾滋病毒(HIV)感染儿童治疗耐多药结核病中的药物动力学和药物相互作用进行了考察。

2018年1月,发表在《Antimicrob Agents Chemother》上的一项研究,对洛匹那韦-利托那韦与一线和二线抗结核药物在艾滋病毒(HIV)感染儿童治疗耐多药结核病中的药物动力学和药物相互作用进行了考察。

背景:洛匹那韦-利托那韦是年轻HIV感染儿童目前一线抗逆转录病毒疗法的主要药物。由于多药耐药性(MDR)结核病(TB)常出现高载量结核的年轻儿童中,因此识别MDR-TB治疗和洛匹那韦-利托那韦之间潜在相互作用很重要。研究人员描述了洛匹那韦-利托那韦与HIV感染儿童MDR-TB治疗常用药物之间的药物动力学和潜在的药物-药物相互作用。

方法:构建一个联合的人群药物动力学模型,共同描述洛匹那韦-利托那韦在32名HIV感染儿童(其中16名MDR-TB接受联合高剂量的异烟肼、吡嗪酰胺、乙胺丁醇、乙硫胺、特立齐酮、氟喹诺酮、阿米卡西治疗和16名无TB)中的药物动力学,这些儿童均是在含有洛匹那韦-利托那韦抗逆转录病毒疗法方案中确认的。将洛匹那韦和利托那韦的一级吸收和消除单室模型合并成一个整合模型。

结果:采用最大抑制模型描述利托那韦浓度对洛匹那韦清除的动态抑制作用。即使在校正异速比例体重作用后,仍发现洛匹那韦和利托那韦暴露存在较大的变异性,并发现洛匹那韦和利托那韦的药物动力学参数之间存在较强的关联。MDR-TB治疗对洛匹那韦或利托那韦的生物利用度、清除率或吸收速率常数没有显著作用。大多数儿童(MDR-TB儿童的81%,对照组的88%)能达到洛匹那韦的治疗谷浓度(1 mg/L)。

结论:洛匹那韦-利托那韦与MDR-TB常用药的联合给药对洛匹那韦或利托那韦的关键药物动力学参数没有显著作用。在该研究中患者间较大的差异以及中等的研究样本数量,这些结果应该被考虑。

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    2019-01-01 xjy02
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    2018-04-11 syscxl
  3. 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  4. 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encryptionId=481a2094a9, topicName=Agent)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b05b180, createdName=grace5700, createdTime=Sat Jul 07 11:05:00 CST 2018, time=2018-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909235, encodeId=326c190923581, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f73a255, createdName=medscijoin, createdTime=Tue Aug 21 10:05:00 CST 2018, time=2018-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779568, encodeId=c3ef1e7956803, content=<a href='/topic/show?id=0473209562' target=_blank style='color:#2F92EE;'>#agents#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2095, encryptionId=0473209562, topicName=agents)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=1072181, createdName=wjywjy, createdTime=Sun Jun 24 16:05:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007587, encodeId=73dd200e587ab, content=<a href='/topic/show?id=754f11418cc' target=_blank style='color:#2F92EE;'>#MDR-TB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11418, encryptionId=754f11418cc, topicName=MDR-TB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Mon Mar 19 22:05:00 CST 2018, time=2018-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455803, encodeId=bf921455803d8, content=<a href='/topic/show?id=c8bd651103a' target=_blank style='color:#2F92EE;'>#洛匹那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65110, encryptionId=c8bd651103a, topicName=洛匹那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a74e5737171, createdName=cathymary, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471577, encodeId=8cc714e15776a, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1560147, encodeId=dab8156014e1e, content=<a href='/topic/show?id=ecf3323007c' target=_blank style='color:#2F92EE;'>#利托那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32300, encryptionId=ecf3323007c, topicName=利托那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e46815077905, createdName=sunyl12, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=)]
    2018-07-07 grace5700
  5. [GetPortalCommentsPageByObjectIdResponse(id=2084342, encodeId=cd132084342d5, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Tue Jan 01 19:05:00 CST 2019, time=2019-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991676, encodeId=5c9b19916e60a, content=<a href='/topic/show?id=b8b11141ed8' target=_blank style='color:#2F92EE;'>#MDR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11417, encryptionId=b8b11141ed8, topicName=MDR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b27406, 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channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2095, encryptionId=0473209562, topicName=agents)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=1072181, createdName=wjywjy, createdTime=Sun Jun 24 16:05:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007587, encodeId=73dd200e587ab, content=<a href='/topic/show?id=754f11418cc' target=_blank style='color:#2F92EE;'>#MDR-TB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11418, encryptionId=754f11418cc, topicName=MDR-TB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Mon Mar 19 22:05:00 CST 2018, time=2018-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455803, encodeId=bf921455803d8, content=<a href='/topic/show?id=c8bd651103a' target=_blank style='color:#2F92EE;'>#洛匹那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65110, encryptionId=c8bd651103a, topicName=洛匹那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a74e5737171, createdName=cathymary, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471577, encodeId=8cc714e15776a, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1560147, encodeId=dab8156014e1e, content=<a href='/topic/show?id=ecf3323007c' target=_blank style='color:#2F92EE;'>#利托那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32300, encryptionId=ecf3323007c, topicName=利托那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e46815077905, createdName=sunyl12, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2084342, encodeId=cd132084342d5, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Tue Jan 01 19:05:00 CST 2019, time=2019-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991676, encodeId=5c9b19916e60a, content=<a href='/topic/show?id=b8b11141ed8' target=_blank style='color:#2F92EE;'>#MDR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11417, encryptionId=b8b11141ed8, topicName=MDR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b27406, 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encryptionId=481a2094a9, topicName=Agent)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b05b180, createdName=grace5700, createdTime=Sat Jul 07 11:05:00 CST 2018, time=2018-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909235, encodeId=326c190923581, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f73a255, createdName=medscijoin, createdTime=Tue Aug 21 10:05:00 CST 2018, time=2018-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779568, encodeId=c3ef1e7956803, content=<a href='/topic/show?id=0473209562' target=_blank style='color:#2F92EE;'>#agents#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2095, encryptionId=0473209562, topicName=agents)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=1072181, createdName=wjywjy, createdTime=Sun Jun 24 16:05:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007587, encodeId=73dd200e587ab, content=<a href='/topic/show?id=754f11418cc' target=_blank style='color:#2F92EE;'>#MDR-TB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11418, encryptionId=754f11418cc, topicName=MDR-TB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Mon Mar 19 22:05:00 CST 2018, time=2018-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455803, encodeId=bf921455803d8, content=<a href='/topic/show?id=c8bd651103a' target=_blank style='color:#2F92EE;'>#洛匹那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65110, encryptionId=c8bd651103a, topicName=洛匹那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a74e5737171, createdName=cathymary, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471577, encodeId=8cc714e15776a, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1560147, encodeId=dab8156014e1e, content=<a href='/topic/show?id=ecf3323007c' target=_blank style='color:#2F92EE;'>#利托那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32300, encryptionId=ecf3323007c, topicName=利托那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e46815077905, createdName=sunyl12, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=)]
    2018-06-24 wjywjy
  7. [GetPortalCommentsPageByObjectIdResponse(id=2084342, encodeId=cd132084342d5, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Tue Jan 01 19:05:00 CST 2019, time=2019-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991676, encodeId=5c9b19916e60a, content=<a href='/topic/show?id=b8b11141ed8' target=_blank style='color:#2F92EE;'>#MDR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11417, encryptionId=b8b11141ed8, topicName=MDR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b27406, 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encryptionId=481a2094a9, topicName=Agent)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b05b180, createdName=grace5700, createdTime=Sat Jul 07 11:05:00 CST 2018, time=2018-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1909235, encodeId=326c190923581, content=<a href='/topic/show?id=8039e2512e8' target=_blank style='color:#2F92EE;'>#相互作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72512, encryptionId=8039e2512e8, topicName=相互作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f73a255, createdName=medscijoin, createdTime=Tue Aug 21 10:05:00 CST 2018, time=2018-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779568, encodeId=c3ef1e7956803, content=<a href='/topic/show?id=0473209562' target=_blank style='color:#2F92EE;'>#agents#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2095, encryptionId=0473209562, topicName=agents)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=1072181, createdName=wjywjy, createdTime=Sun Jun 24 16:05:00 CST 2018, time=2018-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007587, encodeId=73dd200e587ab, content=<a href='/topic/show?id=754f11418cc' target=_blank style='color:#2F92EE;'>#MDR-TB#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11418, encryptionId=754f11418cc, topicName=MDR-TB)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Mon Mar 19 22:05:00 CST 2018, time=2018-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1455803, encodeId=bf921455803d8, content=<a href='/topic/show?id=c8bd651103a' target=_blank style='color:#2F92EE;'>#洛匹那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65110, encryptionId=c8bd651103a, topicName=洛匹那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a74e5737171, createdName=cathymary, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471577, encodeId=8cc714e15776a, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1560147, encodeId=dab8156014e1e, content=<a href='/topic/show?id=ecf3323007c' target=_blank style='color:#2F92EE;'>#利托那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32300, encryptionId=ecf3323007c, topicName=利托那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e46815077905, createdName=sunyl12, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=)]
    2018-03-19 clmlylxy
  8. 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  9. 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content=<a href='/topic/show?id=c8bd651103a' target=_blank style='color:#2F92EE;'>#洛匹那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65110, encryptionId=c8bd651103a, topicName=洛匹那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a74e5737171, createdName=cathymary, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1471577, encodeId=8cc714e15776a, content=<a href='/topic/show?id=c0132410554' target=_blank style='color:#2F92EE;'>#互作#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24105, encryptionId=c0132410554, topicName=互作)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dc87121468, createdName=ylz8405, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1560147, encodeId=dab8156014e1e, content=<a href='/topic/show?id=ecf3323007c' target=_blank style='color:#2F92EE;'>#利托那韦#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32300, encryptionId=ecf3323007c, topicName=利托那韦)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e46815077905, createdName=sunyl12, createdTime=Sun Mar 04 06:05:00 CST 2018, time=2018-03-04, status=1, ipAttribution=)]
    2018-03-04 ylz8405
  10. 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