一种治疗HIV-1感染的新机制药物Fostemsavir

IF 0.4 Q4 PHARMACOLOGY & PHARMACY Journal of Pharmacology & Pharmacotherapeutics Pub Date : 2021-04-01 DOI:10.4103/jpp.jpp_19_21
R. Priyadharsini, C. Divyashanthi, D. Elango
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引用次数: 0

摘要

艾滋病毒是一个死亡率和发病率不断上升的全球性问题。高活性抗逆转录病毒治疗在减少HIV RNA和改善免疫应答方面是有效的。目前方案中的药物存在不良反应、药物不耐受、耐药等缺点。由于需要寻找具有新的作用机制的药物,因此对针对病毒gp120受体的化合物进行了筛选,并从中筛选出了最合适的药物。在一项II期和III期试验中,发现药物BMS-663068 fostemsavir在降低病毒RNA水平方面有效。该药是一种前药,可转化为代谢物temsavir BMS-626529。对于接受过多种治疗方案的多药耐药感染患者,以及由于耐药性和安全性问题而不能耐受该药物方案的患者,首选剂量为600mg口服12小时。该药物由CYP3A4代谢,并与CYP3A4诱导剂和抑制剂有药物相互作用。本文主要综述了fostemsavir的作用机制、临床试验、药理特性和不良反应。
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Fostemsavir, a Drug with Novel Mechanism for the Treatment of HIV-1 Infection
HIV is a global problem with increased mortality and morbidity. The highly active antiretroviral therapy is effective in reducing the HIV RNA and improving the immune response. The drugs in the current regimen have certain disadvantages such as adverse effects, drug intolerance, and drug resistance. Since there is a demand for identifying the drugs with new mechanism of action, the compounds which target the viral gp120 receptor were screened and the most suitable drug among them was identified. In a Phase II and Phase III trial, the drug BMS-663068 fostemsavir was found to be efficacious in reducing the viral RNA levels. The drug is a prodrug that gets converted into metabolite temsavir BMS-626529. The preferred dose is 600 mg orally 12 hourly in patients who had undergone many treatment schedules with multidrug-resistant infection and those who cannot tolerate the drug regimen due to resistance and safety issues. The drug is metabolized by CYP3A4 and has drug interactions with CYP3A4 inducers and inhibitors. This review mainly comprises the mechanism of action, clinical trials, pharmacological properties, and adverse effects of the drug fostemsavir.
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