Anker Mary, Corales Roberto B
Mid Hudson Care Center, Albany Medical Center, 142 Aaron Court, Kingston, New York 12401, USA.
Expert Opin Investig Drugs. 2008 Jan;17(1):97-103. doi: 10.1517/13543784.17.1.97.
Integrase is essential for HIV-1 replication; however, potent inhibition of the isolated enzyme in biochemical assays has not readily translated into antiviral activity in a manner consistent with inhibition of integration. Raltegravir is a novel HIV-1 integrase strand transfer inhibitor with potent in vitro activity against wild-type and multi-class resistant HIV-1 virus (in vitro IC(95) for HIV-1 in 50% normal human serum = 33 nM). Inhibition of integrase prevents insertion of HIV DNA into the human DNA genome, thus blocking the ability of HIV to replicate. Raltegravir is administered orally every 12 h and does not require boosting with low-dose ritonavir (RTV) to achieve therapeutic concentrations. Raltegravir is not a potent inhibitor or inducer of cytochrome P450 3A4, and it is predominantly metabolized by glucuronidation, specifically by the enzyme UDP-glucuronosyltransferase 1A1.
整合酶对于HIV-1复制至关重要；然而，在生化检测中对分离出的该酶的有效抑制尚未以与整合抑制相一致的方式轻易转化为抗病毒活性。雷特格韦是一种新型HIV-1整合酶链转移抑制剂，对野生型和多类耐药HIV-1病毒具有强大的体外活性（在50%正常人血清中对HIV-1的体外IC(95)=33 nM）。整合酶的抑制可防止HIV DNA插入人类DNA基因组，从而阻断HIV复制的能力。雷特格韦每12小时口服一次，无需用低剂量利托那韦（RTV）增强以达到治疗浓度。雷特格韦不是细胞色素P450 3A4的强效抑制剂或诱导剂，它主要通过葡萄糖醛酸化代谢，具体是由尿苷二磷酸葡萄糖醛酸基转移酶1A1进行代谢。
