Pharmacokinetic drug interactions of integrase strand transfer inhibitors.
Pharmacokinetic drug interactions of integrase strand transfer inhibitors.
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DOI：
10.1016/j.crphar.2021.100044
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发表时间：
2021
影响因子：
--
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Lu CH;Bednarczyk EM;Catanzaro LM;Shon A;Xu JC;Ma Q
含有整合酶链转移抑制物(INSTI)的方案目前被认为是治疗人类免疫缺陷病毒(HIV)感染的一线药物。尽管INSTI具有一个共同的作用机制，即不可逆转地抑制HIV整合酶以阻止HIV复制周期，但包括Raltegravir、elvitegravir、Dolutegravir和bitegravir在内的INSTI在药代动力学特征上有所不同。Raltegravir通过UDP-葡萄糖醛酸基转移酶(UGTS)进行生物转化，而elvitegravir主要由细胞色素P450(CYP)3A4代谢，并与考比西坦共同组成药物，以增加其血浆暴露。多洛替格列韦和比替格列韦的代谢途径相似，都包括CYP3A和UGT1A1，两种药物都是不同药物转运体的底物。由于新陈代谢的不同，INSTI通过CYP酶和转运蛋白作为诱导剂或抑制剂与其他药物进行不同的相互作用。这些药物的相互作用可能成为长期临床使用的一个重要考虑因素，因为艾滋病毒携带者(PWH)的预期寿命接近普通人群。此外，常见的老年挑战，如多病和多药治疗，在威斯康星医院越来越被认识到。本文综述了INSTI与INSTI的药代动力学相互作用，以及INSTI药物相互作用的未来前景。
The integrase strand transfer inhibitor (INSTI)-containing regimens are currently considered as the first-line treatment of human immunodeficiency virus (HIV) infection. Although possessing a common mechanism of action to inhibit HIV integrase irreversibly to stop HIV replication cycle, the INSTIs, including raltegravir, elvitegravir, dolutegravir, and bictegravir, differ in pharmacokinetic characteristics. While raltegravir undergoes biotransformation by the UDP-glucuronosyltransferases (UGTs), elvitegravir is primarily metabolized by cytochrome P450 (CYP) 3A4 and co-formulated with cobicistat to increase its plasma exposure. The metabolism pathways of dolutegravir and bictegravir are similar, both including CYP3A and UGT1A1, and both agents are substrates to different drug transporters. Because of their differences in metabolism, INSTIs interact with other medications differently through CYP enzymes and transporters as inducers or inhibitors. These drug interactions may become an important consideration in the long-term clinical use because the life expectancy of people with HIV (PWH) approaches to that of the general population. Also, common geriatric challenges such as multimorbidity and polypharmacy have been increasingly recognized in PWH. This review provides a summary of pharmacokinetic interactions with INSTIs and future perspectives in implications of INSTI drug interactions.