Liedtke Michelle D, Tomlin C Ryan, Lockhart Staci M, Miller Misty M, Rathbun R Chris
Department of Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Infect Drug Resist. 2014 Mar 18;7:73-84. doi: 10.2147/IDR.S40168. eCollection 2014.
Raltegravir is an integrase strand-transfer inhibitor approved for the treatment of HIV infection. It was the first medication in a novel class of antiretroviral agents to be approved for use in the United States in 2007. Raltegravir exhibits potent activity against wild-type HIV-1, but resistance development has been noted through three different pathways. It is metabolized primarily through uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes and exhibits low potential for drug-drug interactions; however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and the most commonly reported adverse effects include headache, nausea, and diarrhea. Serious adverse effects with raltegravir are rare but include rhabdomyolysis and severe skin and hypersensitivity reactions. It has been approved for use in both treatment-naïve and treatment-experienced patients and is a preferred first-line agent in both United States and European HIV treatment guidelines. Although initial approval was granted on 48-week data, 5-year clinical data have recently been published. This article reviews the data supporting long-term efficacy and safety of raltegravir in the treatment of HIV infection.
拉替拉韦是一种整合酶链转移抑制剂，已被批准用于治疗HIV感染。它是2007年在美国获批使用的新型抗逆转录病毒药物类别中的首个药物。拉替拉韦对野生型HIV-1表现出强效活性，但已通过三种不同途径发现了耐药性的产生。它主要通过尿苷二磷酸葡萄糖醛酸基转移酶1A1进行代谢，并有单一的无活性葡萄糖醛酸代谢物。拉替拉韦不是细胞色素P450酶的底物、抑制剂或诱导剂，药物相互作用的可能性较低；然而，强效的尿苷二磷酸葡萄糖醛酸基转移酶1A1抑制剂或诱导剂可改变拉替拉韦的药代动力学。它耐受性良好，最常报告的不良反应包括头痛、恶心和腹泻。拉替拉韦的严重不良反应罕见，但包括横纹肌溶解以及严重的皮肤和超敏反应。它已被批准用于初治和经治患者，在美国和欧洲的HIV治疗指南中均为首选一线药物。尽管最初的批准基于48周的数据，但最近已公布了5年的临床数据。本文综述了支持拉替拉韦治疗HIV感染长期疗效和安全性的数据。
